STK11 and/or KEAP1 genomic alterations showed lack of clinical benefits from addition of immunotherapy to chemotherapy in NSCLC patients


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