Efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in KRAS-mutant advanced non-small cell lung cancer

Objective To compare the anti-tumor efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) presenting with or without KRAS mutation. Methods From October 2015 to October 2019,clinical data about patients with advanced NSCLC who had been administrated with PD-1/PD-L1 ICIs monotherapy in the first medical center of Chinese PLA General Hospital were retrospectively analyzed.A total of 28 KRAS-positive patients (21 males and 7 females with median age of 63 years) and 30 KRAS-negative patients (22 males and 8 females with median age of 67 years) were included.The patients were administrated with Nivolumab (3 mg/kg,intravenous infusion once per two weeks,four weeks as a treatment cycle) or Pembrolizumab (2 mg/kg,intravenous infusion once per three weeks,three weeks as a treatment cycle).Clinical outcomes and adverse events were evaluated among KRAS-mutant and KRAS wild-type patients every 2 treatment cycles. Results Nosignificant difference was observed in objective response rate (ORR,25% vs 20%,P=00.648) and disease control rate (DCR,64.3% vs 63.3%,P=00.940) between the KRAS-mutant group and wild-type group.The follow-up lasted to January 2020.The median PFS was 5.85 months (95% CI:0.00 to 12.26) in KRAS-mutant group compared with 6.74 months (95% CI:3.79 to 9.68) in wild-type group,and the median OS was 17.68 months (95% CI:13.44 to 21.91) in KRAS-mutant group,while 15.70 months (95% CI:2.66 to 28.75) in the KRAS wild-type group,without significant difference (P>0.05).The adverse events profile was similar in the two subgroups,with adverse events rate of 60.7% in the KRAS-mutant group versus 56.7% in the wild-type group (P=00.754). Conclusion PD-1/PD-L1 ICIs are potential and safe therapeutic options for advanced NSCLC patients,regardless of KRAS mutation status.