Previous studies have indicated that STK11 gene alterations cause resistance to immunotherapy in NSCLC patients. In addition, STK11 gene is significantly co-mutated with KEAP1 gene. Nowadays, pembrolizumab (P) plus pemetrexed and either cisplatin or carboplatin (CP) is a standard of care first-line of metastatic EGFR/ALK wild-type (wt) non-squamous non-small cell lung cancer (mnsNSCLC). However, the biomarkers for predicting clinical benefits from patients received chemo-immunotherapy remain poorly defined. A study analyzed mnsNSCLC patients who received PCP or CP from 17 academic institutions in the US and Europe. In PCP-treated patients, the PFS and OS were significantly shorter in patients with STK11 and/or KEAP1 genomic alterations (N=66) compared to STK11 and KEAP1 wild-type (N=73) patients (PFS: 3.6m vs. 8.4m, HR=2.39, 95% CI 1.58-3.63; OS: 10.6m vs. 20.4m, HR=2.0, 95% CI 1.18-3.41). Furthermore, in patients with STK11 and/or KEAP1 genomic alterations, the PFS and OS data showed that the addition of pembrolizumab to CP chemotherapy did not result in clinical benefit compared to CP alone (PFS: 3.6m vs. 4.5m, HR 0.90, 95% CI 0.70-1.16; OS: 9.9m vs. 10.7m, HR 0.99, 95% CI 0.74-1.35). These results revealed that novel treatment strategies are needed in STK11 and/or KEAP1-mutant NSCLC patients.
Skoulidis F, et al. ASCO annual meeting 2019