A retrospective analysis of KEYNOTE-189 trial evaluating pembrolizumab versus placebo in combination with chemotherapy in non-squamous NSCLC did not find any differential benefit with the addition of ICI to chemotherapy in patients with KRAS mutations compared to those without; notably, patients with both KRAS mutant and WT tumors appeared to benefit from combination chemoimmunotherapy compared to chemotherapy alone, though the OS benefit in KRAS mutant tumors did not reach statistical significance (KRAS-WT HR 0.55, 95%: CI 0.37–0.81; KRAS-mutant HR 0.79, 95% CI: 0.45–1.38). 64 A pooled analysis from the FDA of 12 registrational clinical trials of ICI monotherapy or chemoimmunotherapy ( n = 1430, 39% KRAS-mutated, 61% WT) demonstrated similar outcomes in patients with and without KRAS mutations, both when treated with ICI monotherapy or with ICI + chemotherapy. 65 Both KRAS-mutant and KRAS-WT patients had higher ORR and median OS when treated with chemo plus ICI versus ICI alone.
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