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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Thursday, May 12, 2022
According to Howard Jack West, MD, of the City of Hope Comprehensive Cancer Center, Duarte, California, and colleagues, first-line atezolizumab and bevacizumab plus chemotherapy seemed to be efficacious in patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring KRAS mutations and co-occurring STK11, KEAP1, or TP53 mutations and/or high levels of PD-L1 expression. This exploratory subgroup analysis of the phase III IMpower150 trial, which was published in the Journal for ImmunoTherapy of Cancer, also further implicated STK11 and/or KEAP1 mutations as poor prognostic indicators.
Patients were randomly assigned in a 1:1:1 ratio to undergo chemotherapy with carboplatin and paclitaxel plus atezolizumab and/or bevacizumab. They were classified into overlapping mutation-evaluable intention-to-treat (n = 920) and PD-L1 biomarker–evaluable (n = 774) populations.
Atezolizumab and bevacizumab plus chemotherapy and atezolizumab plus chemotherapy demonstrated numerical improvements in the median durations of overall and progression-free survival compared with bevacizumab plus chemotherapy in those with KRAS-mutated disease. In this patient population, the durations of overall and progression-free survival were longer with atezolizumab and bevacizumab plus chemotherapy than with bevacizumab plus chemotherapy across PD-L1 subgroups; however, in the PD-L1–low and PD-L1–negative subgroups, the durations of overall survival with atezolizumab/chemotherapy and bevacizumab/chemotherapy did not seem to differ. The duration of overall survival was prolonged with atezolizumab plus chemotherapy compared with atezolizumab and bevacizumab plus chemotherapy and bevacizumab plus chemotherapy in patients with KRAS wild-type disease across PD-L1 subgroups.
KRAS was found to be frequently co-mutated with STK11, KEAP1, and TP53. Patients with KRAS-mutated disease and co-occurring STK11 and/or KEAP1 mutations seemed to experience inferior overall and progression-free survival outcomes. In those with KRAS-mutated disease and co-occurring STK11 and/or KEAP1 or TP53 mutations, the most prolonged duration of survival was reported with atezolizumab and bevacizumab plus chemotherapy.
“Overall, prospective studies are essential to verify the promising findings observed in this subgroup analysis,” the investigators concluded.
Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.
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