HER2: human epidermal growth factor receptor 2; PD-L1: programmed cell death ligand-1; dMMR: deficient mismatch repair; MSI-H: microsatellite instability-high; pMMR: proficient mismatch repair; CPS: combined positive score; FU: fluorouracil; FOLFOX: oxaliplatin, leucovorin plus bolus and short-term infusional FU; CAPOX/XELOX: capecitabine plus oxaliplatin; TPS: Tumor Proportion Score.
* Refer to text for guidelines for exclusion of patients for trastuzumab on the basis of excess cardiac risk.
¶ Refer to text for discussion of options for backbone cytotoxic regimen to combine with trastuzumab.
Δ While the chemotherapy backbone in the KEYNOTE-590 trial was cisplatin plus FU many clinicians prefer an oxaliplatin-containing regimen (eg, FOLFOX, CAPOX [XELOX]) in this setting.
◊ Although others disagree, we do not routinely recommend immunotherapy for patients with SCC and PD-L1 TPS <1 or CPS <10. However, given the generally greater activity of immune checkpoint inhibitors in SCC as compared with adenocarcinomas, we consider immunotherapy in patients with low PD-L1-expressing SCCs on a case-by-case (eg, young age, intermediate PD-L1 expression [eg, CPS 5 to 9]), emphasizing the uncertainty of benefit, potential toxicity, and financial cost.
§ In our view, there are insufficient data to support first-line use of immunotherapy plus chemotherapy in patients with non-PD-L1 overexpressing tumors that are not dMMR/MSI-H. However, opinion differs on the use of immunotherapy for tumors with a CPS 1-4. Refer to text.
¥ Pembrolizumab monotherapy is an option for asymptomatic nonbulky disease.