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What's new in oncology

What's new in oncology
Authors:
April F Eichler, MD, MPH
Diane MF Savarese, MD
Sadhna R Vora, MD
Sonali Shah, MD
Literature review current through: Feb 2022. | This topic last updated: Feb 25, 2022.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

BREAST CANCER

Carboplatin in neoadjuvant therapy for triple negative breast cancer (February 2022)

The effect of incorporation of carboplatin in neoadjuvant regimens for triple negative breast cancer (TNBC) is being evaluated. In a randomized trial, among patients with stage II to III TNBC receiving anthracycline-based chemotherapy, the addition of carboplatin increased the breast pathologic complete response rate from 46 to 60 percent but did not improve five-year event-free survival or overall survival [1]. However, the study was not powered to assess survival outcomes. In a separate trial, the addition of pembrolizumab to a carboplatin-containing chemotherapy regimen improved event-free survival (overall survival results were immature). Based on these data, our preferred regimen for patients with stage II or III TNBC includes both pembrolizumab and carboplatin. (See "Choice of neoadjuvant chemotherapy for HER2-negative breast cancer", section on 'In an anthracycline-containing regimen'.)

Aromatase inhibitors versus tamoxifen in premenopausal patients on adjuvant ovarian suppression for breast cancer (January 2022)

Ovarian function suppression (OFS) is often added to adjuvant endocrine therapy for premenopausal women with high-risk, hormone receptor (HR)-positive breast cancer, but whether it should be used with tamoxifen versus an aromatase inhibitor (AI) is unclear. In a meta-analysis of four randomized trials including 7000 premenopausal patients with HR-positive breast cancer receiving adjuvant OFS, AI improved 10-year recurrence rates versus tamoxifen (18 versus 15 percent, relative risk [RR] 0.79) [2]. Distant recurrences were also improved (RR 0.83), although breast cancer mortality rates were similar. For premenopausal patients receiving adjuvant OFS for HR-positive breast cancer, we suggest an AI, although tamoxifen is a reasonable alternative. (See "Adjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer", section on 'Rationale for AI over tamoxifen, in combination with OFS'.)

Assessing response to neoadjuvant therapy in breast cancer (January 2022)

Studies are evaluating surrogates for survival outcomes among patients with breast cancer receiving neoadjuvant chemotherapy (NACT), including pathologic complete response (pCR) rates and residual cancer burden (RCB). A meta-analysis of 54 trials of neoadjuvant therapy in over 32,000 breast cancer patients failed to confirm pCR as an adequate surrogate for disease-free survival (DFS) or overall survival (OS) [3]. A separate study demonstrated a correlation between RCB and event-free survival [4]. Although we continue to use pCR to guide adjuvant treatment decisions in patients who have received NACT, RCB can further refine prognostic information. (See "General principles of neoadjuvant management of breast cancer", section on 'Assessment for pathologic complete response'.)

IV placement, venipuncture, and blood pressure measurements after breast cancer surgery (October 2021)

Avoiding lymph node dissection is the only preventive measure proven to reduce the risk of developing lymphedema after breast cancer surgery; however, many patients are told to avoid intravenous catheters, venipunctures, and blood pressure measurements in the arm ipsilateral to the previous surgery for the rest of their lives. In agreement with the American Society of Breast Surgeons, the Society for Ambulatory Anesthesia issued a statement that these measures are not contraindicated in patients who have no lymphedema, even if they have had an axillary lymph node dissection [5]. Our approach is generally consistent with this statement. We support shared decision-making that accounts for the individual's risk factors for developing lymphedema, the clinical situation and monitoring needs, and patient preferences. (See "Breast cancer-associated lymphedema", section on 'Unsupported risk reduction strategies'.)

Adjuvant abemaciclib in high-risk, hormone receptor-positive, HER2-negative breast cancer (October 2021)

For patients with high-risk, hormone receptor (HR)-positive, HER2-negative breast cancer, previous data have shown benefits with adjuvant abemaciclib. Now, in longer follow-up of 27 months, benefits are maintained, both in regard to invasive disease-free survival (three-year rate of 89 versus 83 percent), and distant recurrence-free survival (90 versus 86 percent) [6]. A higher incidence of Grade ≥3 adverse events (AEs) was observed with versus without abemaciclib (50 versus 16 percent, respectively). These data led to US Food and Drug Administration approval of abemaciclib in patients with HR-positive, HER2-negative, node-positive breast cancer at high risk of recurrence and a Ki-67 score ≥20 percent [7], and we suggest the addition of adjuvant abemaciclib to endocrine therapy in this subset. High risk in this instance is defined as either ≥4 involved axillary lymph nodes; or 1 to 3 involved lymph nodes and either tumor grade 3 or size ≥5.0 cm. However, we note that it is also acceptable not to administer this additional treatment, given the toxicity and only short-term supporting data. (See "Adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer", section on 'Patient selection'.)

Neoadjuvant T-DM1 in HER2-positive breast cancer (September 2021)

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that has demonstrated impressive single-agent activity in patients with HER2-positive metastatic breast cancer, but its role in early breast cancer is less clear. In a randomized trial, which included women with HER2-positive breast cancers 2 cm, neoadjuvant single-agent T-DM1 resulted in a similar pathologic complete response rate as docetaxel, trastuzumab, and pertuzumab (44 versus 46 percent) [8]. However, other data have suggested a higher rate of locoregional progression with T-DM1 relative to a standard neoadjuvant chemotherapy regimen that incorporates anti-HER2 antibody therapy. Therefore, pending further data, we do not consider T-DM1 to be a standard neoadjuvant regimen in HER2-positive breast cancer. (See "Neoadjuvant therapy for patients with HER2-positive breast cancer".)

CANCER SCREENING AND PREVENTION

Updated guidelines for cervical cancer screening in patients with HIV (August 2021)

In August 2021, the United States Department of Health and Human Services along with the National Institutes of Health published updated guidelines for the screening of cervical cancer in patients with HIV. In contrast to the previous guideline, cervical cancer screening at the time of HIV diagnosis is now limited to patients age 21 years or older [9]. We also follow these updated guidelines for patients without HIV who are on long-term immunosuppressive therapy (eg, solid organ transplant, allogeneic hematopoietic stem cell transplant, systemic lupus erythematous, and those with inflammatory bowel disease or rheumatologic disease requiring current immunosuppressive treatments). (See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states", section on 'Initial screening' and "Screening for cervical cancer in patients with HIV infection and other immunocompromised states", section on 'HIV-negative immunosuppressed patients'.)

CANCER SURVIVORSHIP

Bupropion for low sexual desire in female cancer survivors (February 2022)

Sexual dysfunction, including low sexual desire, is common among female cancer survivors, but clinical trials evaluating pharmacologic agents are limited. In a randomized trial in over 200 female survivors of breast and gynecologic cancer with low baseline sexual desire, treatment with bupropion at either 150 mg or 300 mg over a 10-week period did not improve sexual desire scores compared with placebo [10]. Our approach for female cancer survivors with low desire is to initially treat underlying physical etiologies and refer patients with persistent symptoms to a mental health and/or sexual therapist. (See "Overview of sexual dysfunction in female cancer survivors", section on 'Decreased libido and arousal'.)

ENDOCRINE TUMORS

Long-term survival in patients with pediatric adrenocortical carcinoma (November 2021)

For pediatric patients with adrenocortical carcinoma (ACC), there are limited data for the long-term prognosis of this rare disease. A prospective, single-arm study of approximately 80 pediatric patients with ACC described the outcomes of stage I patients treated with adrenalectomy; stage II patients treated with adrenalectomy and retroperitoneal lymph node dissection; and stage III or IV patients treated with mitotane and chemotherapy, followed by surgery as clinically indicated [11]. Five-year overall survival rates, according to stage, were 95 percent for stage I; 79 percent for stage II; 95 percent for stage III; and 16 percent for stage IV disease. Although patients with stage III disease had better outcomes relative to those with stage II disease, potentially due to receipt of mitotane and chemotherapy, we consider multiple factors (eg, grade, extent of vascular invasion) in decisions regarding systemic therapy. (See "Treatment of adrenocortical carcinoma", section on 'Management'.)

GASTROINTESTINAL CANCER

Sotorasib for KRAS G12C-mutated advanced pancreatic cancer (February 2022)

Sotorasib, a small molecule that specifically inhibits the KRAS G12C protein, is approved for treatment of KRAS G12C-mutated non-small cell lung cancer. In an updated analysis of a cohort of 38 patients with KRAS G12C-mutated metastatic pancreatic cancer receiving sotorasib on the phase I/II CodeBreak100 study, there were eight partial responses (21 percent), and the disease control rate was 84 percent [12]. Treatment was well tolerated, with grade ≥3 treatment-related adverse events in only six patients. We suggest sotorasib rather than cytotoxic chemotherapy for second-line therapy in patients with metastatic pancreatic cancer and a KRAS G12C mutation. (See "Second-line systemic therapy for advanced exocrine pancreatic cancer", section on 'RAS G12C-mutated tumors'.)

Adding immunotherapy to chemotherapy for advanced biliary tract cancer (February 2022)

For most patients with advanced unresectable biliary tract cancer, gemcitabine plus cisplatin (gem/cis) has become a standard first-line regimen. In the randomized, placebo-controlled TOPAZ-1 trial, the addition of the immune checkpoint inhibitor durvalumab to gem/cis improved overall survival (12.8 versus 11.5 months), progression-free survival, and objective response rate compared with gem/cis alone without a significant increase in treatment-related adverse effects [13]. We consider durvalumab plus gem/cis to be an alternative to gem/cis but not necessarily preferred given the added expense and the small increment in median overall survival seen in the TOPAZ-1 trial. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'Gemcitabine plus cisplatin and durvalumab'.)

Hepatic intraarterial chemotherapy without embolization in unresectable hepatocellular carcinoma (November 2021)

Transarterial chemoembolization (TACE) is a standard treatment for large unresectable hepatocellular carcinomas (HCCs) that are not amenable to local thermal ablation; however, each treatment can cause hepatic arterial and parenchymal ischemic damage leading to hepatic decompensation and inability to carry out repeated procedures. In a Chinese trial comparing repeated courses of multiagent hepatic arterial infusional chemotherapy (HAIC) without embolization versus TACE in 315 patients with unresectable large (≥7 cm) HCCs without macrovascular invasion or extrahepatic spread (81 percent hepatitis B virus-related), patients treated with HAIC had improved survival and less toxicity [14]. However, the trial had important limitations, and the results may not be generalizable to other populations with HCC. Where the technical expertise is available, HAIC is an alternative to TACE for large unresectable HCCs, but we await further studies before concluding that HAIC is preferred. (See "Localized hepatocellular carcinoma: Liver-directed therapies for nonsurgical candidates not eligible for local thermal ablation", section on 'Hepatic intraarterial chemotherapy without embolization'.)

Nivolumab plus ipilimumab for initial therapy of mismatch repair deficient metastatic colorectal cancer (October 2021)

For most patients with nonoperable metastatic colorectal cancer (mCRC) that is deficient mismatch repair (dMMR) without a high tumor burden, first-line pembrolizumab is preferred over cytotoxic chemotherapy because of better efficacy and less toxicity, as shown in the KEYNOTE-177 trial. Additional data on initial immunotherapy using nivolumab and low-dose ipilimumab are available from the nonrandomized phase II CheckMate 142 trial, which demonstrated high initial response rates (62 percent) that were durable (median duration not reached with a median follow-up of 29 months) and low rates of grade 3 or 4 toxicity (22 percent) [15]. Whether these results are better than can be achieved with pembrolizumab monotherapy will require a randomized trial. Nivolumab plus low-dose ipilimumab represents an alternative but not necessarily preferred option for initial immunotherapy in dMMR mCRC. (See "Systemic therapy for nonoperable metastatic colorectal cancer: Selecting the initial therapeutic approach", section on 'Patients with deficient DNA mismatch repair/microsatellite unstable tumors'.)

Ivosidenib approved for advanced IDH1-mutated cholangiocarcinoma (August 2021)

Mutations in one of the isocitrate dehydrogenase (IDH) genes are present in up to 25 percent of advanced cholangiocarcinomas, particularly intrahepatic tumors. The oral IDH1 inhibitor ivosidenib has been approved by the US Food and Drug Administration (FDA) for treatment of adults with previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation, as detected by an FDA-approved test [16]. Approval was based on the randomized placebo-controlled Clar1DHy trial, which showed modestly prolonged survival and durable responses with ivosidenib [17]. Although adverse reactions (nausea, vomiting, fatigue) were common, they were mostly low-grade. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'Ivosidenib for IDH-mutated cholangiocarcinoma'.)

GENITOURINARY ONCOLOGY

Long-term follow-up of erdafitinib in advanced urothelial carcinoma (January 2022)

The gene-targeted therapy erdafitinib has regulatory approval for select patients with metastatic urothelial carcinoma (UC), but long-term follow-up was previously limited. In a phase II trial in over 100 patients with locally advanced or metastatic, treatment-refractory UC harboring alterations in FGFR2 or FGFR3, the objective response rate for erdafitinib was 40 percent at median follow-up of 24 months [18]. No new toxicity profiles were identified. Based on these results, we continue to offer erdafitinib for patients with metastatic UC and susceptible FGFR2 or 3 alterations who have progressed on both platinum-based chemotherapy and checkpoint inhibitor immunotherapy. (See "Treatment of metastatic urothelial cancer of the bladder and urinary tract", section on 'Erdafitinib'.)

Neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) for muscle-invasive bladder cancer (January 2022)

For patients with muscle-invasive bladder cancer (MIBC), the optimal regimen for neoadjuvant chemotherapy prior to radical cystectomy is not established. In a phase III trial of almost 500 patients with MIBC treated with either neoadjuvant or adjuvant chemotherapy, dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) had similar three-year progression-free survival (PFS) compared with gemcitabine plus cisplatin (GC) [19]. However, among those treated with neoadjuvant chemotherapy, dose-dense MVAC improved three-year PFS over GC (66 versus 56 percent). Although further follow-up is necessary, for most patients with MIBC and good performance status who are receiving neoadjuvant chemotherapy prior to radical cystectomy, we continue to suggest neoadjuvant MVAC regimens over GC. (See "Neoadjuvant treatment options for muscle-invasive urothelial bladder cancer", section on 'Choice of chemotherapy regimens'.)

Adjuvant pembrolizumab in localized renal cell carcinoma (December 2021)

In patients with localized renal cell carcinoma (RCC) treated with nephrectomy, adjuvant immunotherapy is being evaluated. In a randomized trial of approximately 1000 patients with clear cell RCC treated with nephrectomy, one year of adjuvant pembrolizumab improved disease-free survival (DFS) compared with placebo (two-year DFS, 77 versus 68 percent), and was well tolerated [20]. Based on these data, the US Food and Drug Administration approved adjuvant pembrolizumab in patients with RCC at intermediate-high or high risk of disease recurrence following nephrectomy [21]. We suggest adjuvant pembrolizumab for those with resected RCC who have an estimated five-year recurrence risk of ≥30 percent. (See "Overview of the treatment of renal cell carcinoma", section on 'Approach to adjuvant therapy'.)

Prostate cancer screening for men with germline pathogenic variants in mismatch repair genes (November 2021)

Individuals who carry germline pathogenic variants (PVs) in cancer predisposition genes involved in DNA repair (eg, BRCA2) are at risk for early-onset aggressive prostate cancer, and they may benefit from early initiation of prostate cancer screening. Interim results from the cohort of men with Lynch syndrome and germline MLH1, MSH2, and MSH6 PVs who were enrolled in the prospective IMPACT study demonstrated a higher prostate cancer incidence among men who were carriers of a germline PV in MSH6 or MSH2, but no cases were identified among carriers of an MLH1 pathogenic variant in this first screening round [22]. These findings support the use of targeted PSA screening in men with Lynch syndrome and MSH2 or MSH6 germline PVs to identify those with clinically significant prostate cancer. Additional study is needed to ascertain whether MLH1 PVs are associated with an increased risk of prostate cancer. (See "Genetic risk factors for prostate cancer", section on 'IMPACT study'.)

Pembrolizumab as initial therapy for metastatic urothelial carcinoma (November 2021)

The United States (US) Food and Drug Administration (FDA) previously conditionally approved the checkpoint inhibitor pembrolizumab for patients with treatment-naïve metastatic urothelial carcinoma (UC), but long-term follow-up data were limited. In extended follow-up of a phase II trial of almost 400 patients with treatment-naïve, platinum-ineligible metastatic UC, the objective response rate for pembrolizumab was 29 percent at a median follow-up of 56 months, and three-year overall survival was 22 percent [23]. Based on these data, the US FDA granted full regulatory approval to pembrolizumab for patients with locally advanced or metastatic UC who are not eligible for any platinum-containing chemotherapy [24], and it remains one of our preferred options in this patient population. (See "Treatment of metastatic urothelial cancer of the bladder and urinary tract", section on 'Pembrolizumab'.)

Adjuvant nivolumab for resected urothelial carcinoma (September 2021)

In a placebo-controlled phase III trial of over 700 patients with urothelial carcinoma (UC) and high-risk disease after radical cystectomy, one year of adjuvant nivolumab improved disease-free survival (median 21 versus 11 months) [25]. These data led to approval by the US Food and Drug Administration (FDA) for adjuvant nivolumab in patients at high risk for recurrence after undergoing radical resection of UC [26]. This includes patients with muscle-invasive or node-positive disease after receiving neoadjuvant chemotherapy, or those with extravesicular extension or node-positive disease who did not receive neoadjuvant chemotherapy and were ineligible for or refused adjuvant cisplatin-based chemotherapy. (See "Adjuvant therapy for muscle-invasive urothelial carcinoma of the bladder", section on 'Adjuvant nivolumab'.)

GYNECOLOGIC ONCOLOGY

Role of HPV on cervical cancer prognosis (February 2022)

In almost all cases, cervical cancer is the result of human papillomavirus (HPV) infection; however, it is unclear if HPV-positive cancer confers a better prognosis than HPV-negative cancer. In a prospective study including over 2800 patients with invasive cervical cancer, HPV-positive compared with HPV-negative cancer was associated with 43 percent relative decrease in mortality [27]. These findings are consistent with patients with head and neck cancer, in whom HPV-related disease is also associated with improved prognosis. Thus, HPV-positive disease may be used along with other factors (eg, disease stage, lymph node status) to counsel patients with cervical cancer about disease prognosis. (See "Management of early-stage cervical cancer", section on 'Prognosis'.)

Trametinib for recurrent, low-grade, serous ovarian carcinoma (February 2022)

For patients with recurrent, low-grade, serous ovarian carcinoma, there is interest in using inhibitors of the mitogen-activated protein (MAP) kinase pathway. Now, in a randomized trial among 260 patients with a mean of 2.9 previous lines of systemic therapy, the MEK inhibitor trametinib improved objective response rates (26 versus 6 percent) and progression-free survival (13.0 versus 7.2 months) compared with standard chemotherapy or endocrine therapy [28]. Overall survival was 38 versus 29 months, respectively, a difference that was not statistically significant. Although trametinib does not yet have regulatory approval for recurrent, low-grade, serous ovarian carcinoma, it is an appropriate treatment strategy for this condition and is commercially available. (See "Management of low-grade, serous carcinomas of the ovary", section on 'Recurrent or metastatic disease'.)

Lenvatinib plus pembrolizumab in advanced endometrial cancer (January 2022)

Although pembrolizumab monotherapy is used in mismatch repair-deficient advanced endometrial cancer after progression on chemotherapy, it is less effective in mismatch repair-proficient (pMMR) platinum-refractory disease. In a randomized trial in patients with advanced endometrial cancer with progression on platinum-based chemotherapy, the multiple-receptor tyrosine kinase inhibitor lenvatinib plus pembrolizumab improved both progression-free and overall survival relative to physician's choice chemotherapy in the overall group, as well as in the subset with pMMR disease [29]. For patients with pMMR advanced endometrial cancer who have recently relapsed on platinum-based chemotherapy, we suggest pembrolizumab and lenvatinib rather than further chemotherapy. (See "Treatment of metastatic endometrial cancer", section on 'Pembrolizumab plus lenvatinib'.)

Image-guided intensity-modulated radiation therapy in cervical cancer (October 2021)

For adjuvant radiation for cervical cancer, newer techniques such as intensity- modulated radiation therapy (IMRT) are being evaluated as less toxic options compared with three-dimensional conformal radiation therapy (3D-CRT). In a randomized trial among 300 patients with cervical cancer undergoing postoperative radiation, disease-free survival was similar with image-guided IMRT versus 3D-CRT (77 versus 81 percent), but three-year cumulative incidence of late toxicity was reduced (28 versus 49 percent) [30]. When adjuvant radiation is indicated for cervical cancer, we suggest image-guided IMRT, but 3D-CRT is an acceptable alternative. (See "Management of early-stage cervical cancer", section on 'RT technique'.)

Pembrolizumab in cervical cancer (October 2021)

The role of immunotherapy in cervical cancer is under investigation. In a phase 3 trial in over 600 patients receiving first-line chemotherapy for persistent, recurrent, or metastatic cervical cancer, those assigned to also receive pembrolizumab versus placebo had improvement in median progression-free survival (10.4 versus 8.2 months) and overall survival rates (50 versus 40 percent at two years) [31]. For patients receiving first-line chemotherapy for recurrent or metastatic cervical cancer, we now suggest the addition of pembrolizumab. (See "Management of recurrent or metastatic cervical cancer", section on 'Incorporation of pembrolizumab'.)

Sentinel lymph node biopsy in vulvar cancer (September 2021)

Sentinel lymph node biopsy (SLNB) can be performed in select patients with stage I or II vulvar cancer and no palpable lymphadenopathy to identify those who can forego inguinofemoral lymphadenectomy. In a prospective study including 322 patients with positive sentinel lymph nodes (SLNs), those with SLN micrometastases undergoing adjuvant radiation (and no lymphadenectomy) had an ipsilateral groin recurrence rate at two years of 1.6 percent [32]. Among those with SLN macrometastases, isolated groin recurrence at two years was more frequent in those treated with radiation alone and no lymphadenectomy (22 percent) compared with lymphadenectomy with or without adjuvant radiation (6.9 percent). These results suggest that patients with micrometastases on SLNB who do not undergo lymphadenectomy may have acceptably low recurrence rates with adjuvant radiation, while those with macrometastases may benefit from lymphadenectomy. (See "Squamous cell carcinoma of the vulva: Staging and surgical treatment", section on 'Sentinel lymph node biopsy'.)

Tisotumab vedotin in metastatic cervical cancer progressive on chemotherapy (September 2021)

Tisotumab vedotin is a tissue factor-directed antibody and microtubule inhibitor drug conjugate. In a single arm, open-label study in 101 patients with metastatic or recurrent cervical cancer previously treated with chemotherapy, the agent was associated with a response rate of 24 percent, including 7 percent with complete responses [33]. Based on these results, tisotumab vedotin was approved by the US Food and Drug Administration for recurrent or metastatic cervical cancer that has progressed on chemotherapy [34], and we consider it to be one of several appropriate options in this setting. (See "Management of recurrent or metastatic cervical cancer", section on 'Second-line therapy'.)

Updated version of the AJCC TNM staging for cervical cancer (August 2021)

An updated version of the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for cervical cancer was published in March 2021 and is available separately [35]. This version is now in alignment with the 2018 International Federation of Gynecology and Obstetrics cervical cancer staging system (table 1). Both systems are acceptable staging systems and widely used. (See "Invasive cervical cancer: Staging and evaluation of lymph nodes", section on 'Staging system'.)

HEAD AND NECK CANCER

Concurrent chemoradiation for squamous cell carcinoma of the head and neck (December 2021)

For most patients with squamous cell carcinoma of the head and neck (HNSCC), concurrent chemoradiation (CRT) is standard treatment, but overall survival (OS) data have been lacking. In longer-term follow-up of a meta-analysis including 107 randomized trials and almost 20,000 patients with locoregionally advanced HNSCC, concurrent CRT improved OS over definitive locoregional therapy (surgery and/or radiation [RT]; HR 0.83) [36]. A sustained OS benefit was only seen in those under the age of 70 years. Based on these data, for patients with locoregionally advanced HNSCC under the age of 70, we suggest concurrent CRT rather than definitive locoregional therapy. For many adults age 70 years or older, we suggest RT alone rather than CRT. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Chemotherapy plus definitive locoregional therapy'.)

Pembrolizumab for metastatic nasopharyngeal carcinoma (November 2021)

For patients with recurrent or metastatic nasopharyngeal cancer (NPC), checkpoint inhibitor immunotherapy is an available treatment option, but it has not been directly compared against standard chemotherapy. In a randomized phase III trial of over 200 patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy [37], pembrolizumab did not improve overall survival but had lower toxicity compared with chemotherapy (gemcitabine, capecitabine, or docetaxel). Based on these data, pembrolizumab continues to be an option for patients with metastatic or recurrent NPC that is platinum-refractory, and we prefer its use in those who wish to avoid chemotherapy-related toxicity. (See "Treatment of recurrent and metastatic nasopharyngeal carcinoma", section on 'Pembrolizumab'.)

Screening for oral cavity cancer (October 2021)

Visual screening of the oral cavity (OC) is frequently used to identify squamous cell carcinoma (SCC) and can improve disease-specific survival, but studies with long-term follow-up are limited. In a randomized trial of approximately 200,000 patients in India, at up to nine years of follow-up, visual screening of the OC reduced oral SCC mortality by 27 percent in all patients and by 29 percent in ever-tobacco and/or ever-alcohol users [38]. These and other data continue to support the use of routine mouth examinations to identify and treat SCC of the OC, including individuals with high-risk exposures such as tobacco or alcohol. (See "Chemoprevention and screening in oral dysplasia and squamous cell head and neck cancer", section on 'Screening'.)

MELANOMA AND OTHER SKIN CANCER

Adjuvant pembrolizumab for high-risk node-negative melanoma (November 2021, Modified January 2022)

Although patients with resected, node-negative (Stage IIB and IIC) cutaneous melanoma are at risk for disease recurrence, there was previously no approved adjuvant therapy. In a phase III trial of almost 1000 patients with resected Stage IIB and IIC disease, one year of adjuvant pembrolizumab improved 18-month recurrence-free survival compared with placebo (86 versus 77 percent) [39,40]. Based on these data, the US Food and Drug Administration (FDA) approved adjuvant pembrolizumab for pediatric (12 years and older) and adult patients with Stage IIB and IIC melanoma after complete resection, and we suggest its use in these patients. (See "Adjuvant and neoadjuvant therapy for cutaneous melanoma", section on 'Pembrolizumab versus surveillance'.)

Long-term follow-up of nivolumab plus ipilimumab for melanoma brain metastases (November 2021)

For patients with metastatic melanoma, immunotherapy with nivolumab plus ipilimumab is effective against central nervous system (CNS) metastases, but long-term follow-up of overall survival (OS) was previously limited. In the final analysis of a phase II trial (CheckMate-204) in over 100 patients with metastatic melanoma and asymptomatic CNS metastases treated with nivolumab plus ipilimumab, at median follow-up of 34 months, intracranial objective and complete response rates were 54 and 33 percent, respectively, and three-year OS was 72 percent [41]. Based on these and other data, nivolumab plus ipilimumab continues to be an acceptable treatment option for systemic therapy-naïve patients with metastatic melanoma and small, minimally symptomatic or asymptotic untreated CNS metastases. (See "Management of brain metastases in melanoma", section on 'Asymptomatic brain metastases'.)

Nivolumab plus ipilimumab versus targeted therapy in metastatic BRAF-mutant melanoma (January 2021)

For patients with metastatic melanoma and a BRAF mutation, treatment options include checkpoint inhibitor immunotherapy and targeted therapy with BRAF plus MEK inhibitors, but the optimal sequencing of these agents was not previously established. In a randomized phase III trial (DREAMseq) in over 250 patients with treatment-naïve BRAF mutant melanoma, initial treatment with nivolumab plus ipilimumab, followed by targeted therapy with dabrafenib plus trametinib upon disease progression, improved overall survival (OS) compared with the opposite sequencing of therapy (two-year OS 72 versus 52 percent) [42]. Based on these data, for patients with treatment-naïve metastatic melanoma and a BRAF mutation, we recommend combination immunotherapy with nivolumab plus ipilimumab rather than targeted therapy. (See "Systemic treatment of metastatic melanoma with BRAF and other molecular alterations", section on 'Choice of initial therapy'.)

NEUROONCOLOGY

Progressive parkinsonism after BCMA-targeted CAR-T cell therapy (January 2022)

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known acute and usually reversible complication of chimeric antigen receptor T (CAR-T) cell therapy, but long-term neurologic effects have not been well documented. A recent case report described the onset of progressive parkinsonism approximately 100 days after administration of ciltacabtagene autoleucel, an investigational CAR-T cell therapy for multiple myeloma targeting B-cell maturation antigen (BCMA) [43]. Based on postmortem studies, the syndrome appeared to be an on-target effect of CAR-T cells on BCMA-expressing astrocytes and neurons in the basal ganglia. Delayed parkinsonism has also been reported after idacabtagene vicleucel, another BCMA-targeted product. Further studies are needed to understand risk factors and treatment strategies. (See "Immune effector cell-associated neurotoxicity syndrome (ICANS)", section on 'Delayed parkinsonism'.)

Radiation fields in children >3 years with average-risk medulloblastoma (November 2021)

Results of a recent multicenter randomized trial in children with medulloblastoma support providing lower doses of radiation therapy (RT) to some areas of normal brain without sacrificing tumor control. In the Children's Oncology Group ACNS0331 trial, 549 patients age 3 to 21 years with average-risk medulloblastoma were treated with craniospinal RT plus a boost to either the entire posterior fossa (standard) or to the tumor bed only (narrower volume) [44]. Survival outcomes were similar between groups, and there were no local failures outside the narrower boost volume. Thus, use of a boost confined to the tumor bed plus a margin is now appropriate for patients receiving craniospinal RT for medulloblastoma. (See "Treatment and prognosis of medulloblastoma", section on 'Average-risk disease in children ≥3 years of age'.)

No benefit of carboplatin during radiation for high-risk medulloblastoma (November 2021)

Patients with medulloblastoma who undergo partial resection or have disseminated disease at the time of diagnosis have poor outcomes, and there has been interest in intensified treatment regimens. In the Children's Oncology Group ACNS0332 trial, nearly 300 such children age 3 to 18 years with high-risk medulloblastoma were randomly assigned to receive craniospinal radiation and weekly vincristine with or without daily carboplatin, followed by six cycles of maintenance chemotherapy [45]. With a median follow-up of nearly seven years, carboplatin did not improve event-free or overall survival, and toxicity was greater. A subgroup analysis showing possible benefit in group 3 tumors requires prospective confirmation. (See "Treatment and prognosis of medulloblastoma", section on 'High-risk disease in children ≥3 years of age'.)

Selumetinib, a MEK1/2 inhibitor, in optic pathway gliomas (November 2021)

Optic pathway gliomas (OPGs) in children often harbor BRAF alterations, and case reports have suggested that MEK1/2 or BRAF inhibitors may be an effective therapeutic approach. In a multicenter phase 2 trial that included 25 children with recurrent/progressive sporadic OPG or hypothalamic low-grade glioma treated with selumetinib, an oral MEK1/2 inhibitor, two-year progression-free survival was 74 percent, and visual acuity improved or remained stable in the majority of patients [46]. In a previously reported subset, selumetinib also showed activity in neurofibromatosis type 1 (NF1)-associated OPGs. These data add support for the use of MEK1/2 inhibitors in refractory OPGs, and randomized trials are investigating selumetinib versus chemotherapy in the upfront setting. (See "Optic pathway glioma", section on 'Role of targeted therapies'.)

PALLIATIVE AND SUPPORTIVE CARE

Prophylactic treatment for airway secretions at the end of life (October 2021)

Excess airway secretions in patients at the end of life (death rattle) can be a troublesome symptom for caregivers and loved ones, but recommendations for treatment have been limited by lack of clinical trial data. In a randomized trial conducted in 162 patients in six hospices in the Netherlands, patients entering the dying phase were assigned to receive either prophylactic subcutaneous scopolamine butylbromide (not available in United States) or placebo [47]. Death rattle occurred in a smaller percentage of patients in the scopolamine group (13 versus 27 percent). These results support the efficacy of anticholinergic agents for palliative management of airway secretions in patients nearing the end of life. We prefer glycopyrrolate. (See "Palliative care: The last hours and days of life", section on 'Airway secretions'.)

SOFT TISSUE AND BONE TUMORS

Avapritinib for treatment-refractory gastrointestinal stromal tumors with PDGFRA exon 18 D842V mutations (October 2021)

For patients with advanced gastrointestinal stromal tumor (GIST), novel agents are being evaluated in the treatment-refractory setting. In a phase III trial of almost 500 patients with unresectable or metastatic treatment-refractory GIST, the tyrosine kinase inhibitor (TKI) avapritinib resulted in similar progression-free survival (PFS) compared with the antiangiogenesis agent, regorafenib [48]. However, among 13 patients whose tumors harbored a platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation, avapritinib improved progression-free survival (median not reached versus 4.5 months). Objective response rates in this subset were 43 versus 0 percent. Based on these data, we consider avapritinib to be an acceptable option for patients with PDGFRA D842V mutation-positive GIST who have experienced progression on both imatinib and sunitinib. (See "Tyrosine kinase inhibitor therapy for advanced gastrointestinal stromal tumors", section on 'Avapritinib'.)

Nab-sirolimus for malignant perivascular epithelioid cell differentiation (PEComa) (January 2021)

Mechanistic (mammalian) target of rapamycin (mTOR) inhibitors have shown promise for advanced perivascular epithelioid cell differentiation (PEComa). In an open-label phase II trial in approximately 30 patients with locally advanced unresectable or metastatic malignant PEComa, the mTOR inhibitor nab-sirolimus was associated with an overall response rate of 39 percent [49]. Based on these data, the US Food and Drug Administration (FDA) approved nab-sirolimus in adult patients with locally advanced unresectable or metastatic malignant PEComa. For those without access to nab-sirolimus, other mTOR inhibitors (sirolimus, everolimus, and temsirolimus) are reasonable alternatives. (See "Systemic treatment of metastatic soft tissue sarcoma", section on 'Nab-sirolimus'.)

THORACIC ONCOLOGY

Dabrafenib and trametinib in BRAF-mutant NSCLC (January 2022)

The combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib has previously shown benefit in BRAF-mutant melanomas, but its role in non-small cell lung cancer (NSCLC) is being evaluated. In a phase II study in 93 patients with advanced NSCLC with the BRAF V600E mutation, the combination of dabrafenib plus trametinib was associated with an objective response rate of 68 percent in previously treated patients and 64 percent in treatment-naïve patients [50]. For most patients with advanced NSCLC whose tumors harbor a BRAF V600 mutation, we suggest front-line use of the combination of dabrafenib plus trametinib, rather than chemotherapy and/or immunotherapy. (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer", section on 'BRAF V600E mutation'.)

Postoperative radiation therapy in resected stage III N2 NSCLC (January 2022)

Among patients with stage III N2 non-small cell lung cancer (NSCLC) who have undergone complete surgical resection, the use of postoperative radiation therapy (PORT) is controversial. In the Lung ART trial, among over 500 patients with completely resected NSCLC with pathologically proven N2 disease, those assigned to PORT versus no PORT experienced similar disease-free and overall survival [51]. However, more adverse effects were observed in the PORT group, particularly cardiopulmonary toxicity. Based on these and previous data, for patients with completely resected N2 disease, some UpToDate experts do not offer PORT, while others offer it to very select high-risk patients. (See "Management of stage III non-small cell lung cancer", section on 'Those with N2 involvement diagnosed at surgery'.)

Nivolumab in pleural mesothelioma (November 2021)

For patients with platinum-refractory pleural mesothelioma, immunotherapy has shown improvements in response rates over chemotherapy. In a randomized trial among 332 patients with platinum-refractory mesothelioma (95 percent of whom had pleural mesothelioma), those assigned to nivolumab versus placebo experienced improvements in both progression-free survival (3.0 versus 1.8 months) and overall survival (10.2 versus 6.9 months) [52]. Chemotherapy was not included as a comparator. We continue to consider either immunotherapy or single-agent chemotherapy to be appropriate options for patients with platinum-refractory pleural mesothelioma. (See "Systemic treatment for unresectable malignant pleural mesothelioma", section on 'Immunotherapy'.)

Adjuvant immunotherapy in resectable NSCLC (July 2021, Modified November 2021)

The role of immunotherapy in resectable non-small cell lung cancer (NSCLC) was previously undefined. In a randomized trial in almost 900 patients with stage II to IIIA NSCLC who had undergone surgery and adjuvant chemotherapy, those randomly assigned to atezolizumab had improved disease-free survival relative to the best supportive care group (42 versus 35 months, hazard ratio [HR] 0.79), with greater benefits among those with tumor PD-L1 ≥1 percent (not evaluable versus 35 months; HR 0.66) [53]. Based on these data, atezolizumab is approved by the US Food and Drug administration (FDA) as adjuvant treatment following resection and platinum-based chemotherapy for adults with stage II to IIIA NSCLC whose tumors have programmed cell death ligand 1 (PD-L1) expression on ≥1 percent of tumor cells, as determined by an FDA-approved test [54]. (See "Systemic therapy in resectable non-small cell lung cancer", section on 'Adjuvant immunotherapy for PD-L1-positive disease'.)

Fam-trastuzumab deruxtecan in HER2-mutated advanced NSCLC (October 2021)

There is interest in trastuzumab antibody-based conjugates, such as fam-trastuzumab deruxtecan, in advanced HER2-driven non-small cell lung cancer (NSCLC). In a phase 2 study of 91 patients with HER2 mutation-positive NSCLC that had progressed on standard treatment, the agent was associated with a median progression-free survival of 8.2 months, overall survival of 17.8 months, and response rate of 55 percent [55]. Notable toxicities included drug-related interstitial lung disease in 24 patients (2 fatalities). For patients with HER2-mutated advanced NSCLC that have progressed on standard therapy, fam-trastuzumab deruxtecan is an appropriate, though potentially toxic, off-label option. (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer", section on 'HER2 mutations and amplifications'.)

OTHER ONCOLOGY

Booster doses of COVID-19 vaccines for individuals 12 years or older (October 2021, Modified February 2022)

Several countries have introduced booster doses of COVID-19 vaccines because of potentially attenuated vaccine effectiveness due to waning efficacy and variants. The US Food and Drug Administration has authorized and the Centers for Disease Control and Prevention (CDC) recommends a booster dose for all individuals 12 years or older [56-59]. The booster dose is given five months after a primary BNT162b2 (Pfizer) or mRNA-1273 (Moderna) series for most patients (or three months after the primary series for immunocompromised patients) and two months after a primary Ad26.COV2.S (Johnson & Johnson) series. Any vaccine authorized for the patient's age group can be used for the booster dose, regardless of the vaccine used for the primary series; in general, we favor one of the mRNA vaccines over Ad26.COV2.S. We recommend booster doses for eligible individuals, based on trials and observational evidence suggesting improved vaccine efficacy following a booster dose. (See "COVID-19: Vaccines", section on 'Role of booster vaccinations/waning efficacy'.)

Additional COVID-19 vaccine primary series dose for immunocompromised individuals (August 2021, Modified February 2022)

COVID-19 vaccines are less effective among patients with certain immunocompromising conditions than in the general population; additional vaccine doses have been associated with improved effectiveness in this population. We agree with recommendations from the Advisory Committee on Immunization Practices (ACIP) in the United States that individuals with such conditions (table 2) receive an additional mRNA vaccine dose as part of their primary COVID-19 vaccine series (eg, following two doses of an mRNA vaccine or one dose of Ad26.COV2.S vaccine) [60,61]. This additional primary series dose is distinct from the booster dose, which such patients should additionally receive, although at a shorter interval than recommended for the general population. (See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

Third mRNA COVID-19 vaccine dose and Omicron immunogenicity among cancer patients (January 2022, Modified January 2022)

The Omicron variant of SARS-CoV-2 partially evades vaccine-induced immunity, but for mRNA COVID-19 vaccine recipients in the general population, a third vaccine dose increases neutralizing activity against Omicron; comparable data in cancer patients are lacking. In a prospective cohort study, a third vaccine dose of the mRNA vaccine BNT162b2 was associated with a higher likelihood of detectable neutralizing activity against Omicron in patients with cancer, although the benefit was less in patients with blood cancer compared with those with solid tumors [62]. These data support administering a third dose of mRNA vaccine for patients with active cancer; such patients are also eligible subsequently for a booster dose. (See "COVID-19: Considerations in patients with cancer".)

Routine premedication for PEGylated asparaginase (January 2022)

Asparaginase, a polypeptide of bacterial origin, is an important component of treatment for acute lymphoblastic leukemia, and PEGylated products (eg, pegaspargase, calaspargase) are now preferred for newly diagnosed patients. While they are less immunogenic than nonpegylated E. coli-derived asparaginase, infusion reactions still occur in up to one-third of patients. In 2021, the pegaspargase United States prescribing information was updated to recommend routine premedication with acetaminophen, an H1-receptor blocker, and an H2-receptor blocker administered 30 to 60 minutes prior to each dose [63]. The prescribing information for calaspargase has also been similarly updated [64]. (See "Infusion reactions to systemic chemotherapy", section on 'Asparaginase'.)

Immunogenicity of available vaccines against SARS-CoV-2 in patients with cancer (January 2022)

Patients with cancer are considered to be at high risk for SARS-CoV-2 infection, but there are limited studies directly comparing available COVID-19 vaccines. In an observational cohort study (CANVAX) of over 700 patients with solid organ or hematologic cancers, two doses of an mRNA vaccine (either BNT162b2/Pfizer-BioNTech or mRNA-1273/Moderna) were associated with higher protective immune responses compared with one dose of the adenoviral vector vaccine Ad26.COV2.S/Janssen [65]. Although clinical outcomes were not measured, other studies in the general population suggest that mRNA vaccines may have greater effectiveness against severe disease. In patients with cancer receiving COVID-19 vaccination, as for the general population, we suggest an mRNA COVID vaccine, rather than an adenoviral vector vaccine. (See "COVID-19: Considerations in patients with cancer", section on 'Safety and efficacy' and "COVID-19: Vaccines", section on 'Indications and vaccine selection'.)

New naming convention for therapeutic monoclonal antibodies (January 2022)

The number of therapeutic monoclonal antibodies (mAbs) continues to increase. In order to reduce sound-alikes and specify structural components of the immunoglobulins, the World Health Organization International Nonproprietary Names (INN) Programme has developed four new suffixes to be used instead of "mab" for antibodies developed from 2022 onward [66]. Unmodified immunoglobulins will end in "tug"; mAbs with an engineered constant region will end in "bart"; bifunctional mAbs will end in "mig"; and variable region fragments will end in "ment." (See "Overview of therapeutic monoclonal antibodies", section on 'Naming convention for therapeutic mAbs'.)

COVID-19 vaccination and hematopoietic cell transplant or CAR-T therapy (November 2021)

Immunocompromised individuals who are recipients of hematopoietic cell transplantation (HCT) or chimeric antigen receptor (CAR)-T-cell therapies are at risk for a suboptimal immune response to COVID-19 vaccination. Updated guidance from the United States Centers for Disease Control and Prevention (CDC) now recommends revaccination with a full primary series for patients who were vaccinated prior to receiving HCT or CAR-T-cell therapy and who are at least three months post-HCT or CAR-T-cell therapy. Our recommendations are in agreement with this guidance [67]. (See 'COVID-19: Considerations in patients with cancer', section on 'COVID-19 vaccination' and 'Immunizations in hematopoietic cell transplant candidates and recipients', section on 'COVID-19 vaccine'.)

Comprehensive geriatric analysis in cancer patients (November 2021)

Comprehensive geriatric assessment (CGA) is being evaluated to decrease toxicity from chemotherapy in older adults. In a randomized trial among patients age ≥70 with incurable solid tumors or lymphoma starting a new systemic therapy, the CGA intervention reduced grade ≥3 adverse events compared with usual care (51 versus 71 percent) [68]. Based on these and other data, we utilize a CGA prior to initiation of anticancer therapy in patients ≥65 years. (See "Comprehensive geriatric assessment for patients with cancer", section on 'Supporting evidence'.)

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Topic 8361 Version 10977.0

References

1 : CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer.

2 : Aromatase inhibitors versus tamoxifen in pre-menopausal women with estrogen receptor positive early stage breast cancer treated with ovarian suppression: A patient level meta-analysis of 7,030 women in four randomized trials.

3 : Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis.

4 : Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients.

5 : Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients.

6 : Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study.

7 : Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study.

8 : Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients With ERBB2-Positive Breast Cancer: A Phase 2 Randomized Clinical Trial.

9 : Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients With ERBB2-Positive Breast Cancer: A Phase 2 Randomized Clinical Trial.

10 : Randomized Controlled Phase II Evaluation of Two Dose Levels of Bupropion Versus Placebo for Sexual Desire in Female Cancer Survivors: NRG-CC004.

11 : Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol.

12 : Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol.

13 : Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol.

14 : Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Transarterial Chemoembolization for Large Hepatocellular Carcinoma: A Randomized Phase III Trial.

15 : First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study.

16 : First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study.

17 : Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial.

18 : Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study.

19 : Dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for patients with muscle-invasive bladder cancer (MIBC): Results of the GETUG/AFU VESPER V05 phase III trial

20 : Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma.

21 : Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma.

22 : A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

23 : First-line pembrolizumab (pembro) in cisplatin-ineligible patients with advanced urothelial cancer (UC): Response and survival results up to five years from the KEYNOTE-052 phase 2 study.

24 : First-line pembrolizumab (pembro) in cisplatin-ineligible patients with advanced urothelial cancer (UC): Response and survival results up to five years from the KEYNOTE-052 phase 2 study.

25 : Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.

26 : Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.

27 : Human Papillomavirus Infection Determines Prognosis in Cervical Cancer.

28 : Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial.

29 : Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer.

30 : Late Toxicity After Adjuvant Conventional Radiation Versus Image-Guided Intensity-Modulated Radiotherapy for Cervical Cancer (PARCER): A Randomized Controlled Trial.

31 : Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer.

32 : Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer.

33 : Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study.

34 : Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study.

35 : The new (Version 9) American Joint Committee on Cancer tumor, node, metastasis staging for cervical cancer.

36 : Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group.

37 : Results of KEYNOTE-122: A phase III study of pembrolizumab (pembro) monotherapy vs chemotherapy (chemo) for platinum-pretreated, recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC)

38 : Risk-Based Selection of Individuals for Oral Cancer Screening.

39 : Pembrolizumab versus placebo after complete resection of high-risk stage II melanoma: Efficacy and safety results from the KEYNOTE-716 double-blind phase III trial

40 : Pembrolizumab versus placebo after complete resection of high-risk stage II melanoma: Efficacy and safety results from the KEYNOTE-716 double-blind phase III trial

41 : Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study.

42 : DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): A phase III trial—ECOG-ACRIN EA6134.

43 : Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy.

44 : Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma.

45 : Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children's Oncology Group.

46 : A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study.

47 : Effect of Prophylactic Subcutaneous Scopolamine Butylbromide on Death Rattle in Patients at the End of Life: The SILENCE Randomized Clinical Trial.

48 : Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study.

49 : Long-term follow-up for duration of response (DoR) after weekly nab-sirolimus in patients with advanced malignant perivascular epithelioid cell tumors (PEComa): Results from a registrational open-label phase II trial, AMPECT.

50 : Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis.

51 : Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): an open-label, randomised, phase 3 trial.

52 : Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial.

53 : Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial.

54 : Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial.

55 : Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.

56 : Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.

57 : Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.

58 : Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.

59 : Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.

60 : Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.

61 : Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.

62 : Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer

63 : Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer

64 : Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer

65 : Immunogenicity and Reactogenicity of SARS-CoV-2 Vaccines in Patients With Cancer: The CANVAX Cohort Study.

66 : New INN nomenclature for monoclonal antibodies.

67 : New INN nomenclature for monoclonal antibodies.

68 : Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study