Systemic therapy for A/R/M head & neck cancer
toxicity, HNSCC, pembrolizumab
CPS
The currently preferred first-line treatment for recurrent, unresectable or metastatic HNSCC is pembrolizumab as monotherapy or in combination with platinum and 5-fluorouracil chemotherapy, per the results of KEYNOTE-048 [Combining pembrolizumab with chemotherapy may not be the ideal strategy for increasing pembrolizumab response. Although the KEYNOTE-048 study did not aim to directly compare the two arms, there are a few observations worth considering. First, the addition of chemotherapy as utilized in KEYNOTE-048 likely contributed to the observed increases in toxicity compared with pembrolizumab alone. Second, the median duration-of-response for patients responding to pembrolizumab monotherapy was high compared with the control cetuximab chemotherapy arm (22.6 vs 4.2 months in CPS ≥20, 23.4 vs 4.5 months in CPS ≥1 and 22.6 vs 4.5 months in the total population). Finally, the median duration-of-response for patients who responded to pembrolizumab combined with chemotherapy was much lower (7.1 vs 4.2 months in CPS ≥20 and 6.7 vs 4.3 months for both the CPS ≥1 group and the total population), suggesting the absence of a significant synergistic interaction or immunosensitizing effect of the chemotherapy regimen. These findings highlight the limitations of current standard of care immunotherapy-based regimens for first-line treatment of A/R/M HNSCC and the need to investigate combinations of immunotherapy-based systemic regimens with other potentially immunosensitizing therapies. A review of actively recruiting clinical studies investigating ICIs in combination with different immunosensitizing therapies is summarized in 