Efficacy of chemotherapy plus immune checkpoint inhibitors in first-line treatment of KRAS mutant advanced lung adenocarcinoma
Objective To compare the efficacy and safety of pemetrexed+carboplatin/nedaplatin chemotherapy plus programmed cell death-1(PD-1)inhibitor versus plus bevacizumab in the first-line treatment of KRAS mutant advanced lung adenocarcinoma,and to investigate the influence of PD ligand-1(PD-L1)level on the therapeutic efficacy of pemetrexed+carboplatin/nedaplatin chemotherapy plus PD-1 inhibitor.Methods Seventy-two patients were initially diagnosed with KRAS mutant advanced lung adenocarcinoma in Henan Provincial People's Hospital from October 2019 to June 2023,among whom 38 patients received pemetrexed+carboplatin/nedaplatin chemotherapy plus PD-1 inhibitor(immunotherapy group)and 34 patients received pemetrexed+carboplatin/nedaplatin chemotherapy plus bevacizumab(anti-angiogenic therapy group).The objective response rate(ORR),disease control rate(DCR)after 4 cycles of treatment and occurrence of adverse reactions were compared between two groups.The patients were followed up till March 1,2024,to record the progression-free survival(PFS)and overall survival(OS).The patients in immunotherapy group were divided into positive group(PD-L1 ≥1％)and negative group(PD-L1＜1％),and the ORR,DCR,PFS and OS were compared between positive and negative groups after 4 cycles of treatment.Results(1)There were no significant differences in ORR and DCR between immunotherapy group(44.7％,84.2％)and anti-angiogenic therapy group(35.3％,76.5％)(x2=0.665,P=0.415;x2=0.039,P=0.844).The median PFS and median OS were longer in immunotherapy group[7.9 months(95％CI:5.8-10.0 months),19.8 months(95％CI:14.8-24.8 months)]than those in anti-angiogenic therapy group[5.2 months(95％CI:4.6-5.7 months),14.2 months(95％CI:10.2-18.2 months)](P=0.040,P=0.046).(2)The incidence of thyroid dysfunction was higher in immunotherapy group(15.8％)than that in anti-angiogenic therapy group(0)(P＜0.05),the incidence of hypertension was lower in immunotherapy group(2.6％)than that in anti-angiogenic therapy group(35.3％)(P＜0.05),and there were no significant differences in the incidences of granulocytopenia,thrombocytopenia and other adverse reactions between two groups(P＞0.05).(3)There were no significant differences in the ORR,DCR,median PFS and median OS between positive and negative groups(P＞0.05).Conclusion Both pemetrexed+carboplatin/nedaplatin chemotheray plus PD-1 inhibitor and plus bevacizumab have good short-term efficacy and safety in patients with KRAS mutant advanced lung adenocarcinoma,and chemotherapy plus PD-1 inhibitor can prolong PFS and OS without being affected by PD-L1 expression.
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