Optimal immunotherapy regimens for NSCLC patients with KRAS mutations: a systematic review and network meta-analysis

Abstract

Abstract Objective Patients with KRAS-mutated NSCLC will have a lower survival rate than patients with KRAS gene wild-type, for whom the use of immune checkpoint inhibitors has a significant benefit. We conducted a systematic evaluation and network meta-analysis to find the best treatment option for such patients with ICIs by comparing the efficacy of immune checkpoint inhibitors (PD-1/PD-L1 inhibitors as well as CALT-4 inhibitors) in patients with advanced or metastatic NSCLC with KRAS mutations.Method Until October 30, 2022, a systematic searched of Pubmed, Embase, Cochrane library and Web of Science. The primary endpoint were overall survival (OS) and progression-free survival (PFS) of KRAS-mutated patients treated with immune checkpoint inhibitors compare with chemotherapy. All statistical were made with R-studio.Result Overall, 6 studies that included a total 469 patients were analyzed in this meta-analysis. Pembrolizumab monotherapy had a higher OS than chemotherapy (HR 0.42, 95% CI 0.22, 0.8) and pembrolizumab combined with chemotherapy had a higher PFS than chemotherapy (HR 0.47 95% CI 0.29,0.76). In terms of OS, among NSCLC patients with KRAS-mutated, pembrolizumab monotherapy was the best treatment for their first-line treatment and nivolumab was the best treatment for second-line treatment. In contrast, atezolizumab monotherapy had no significant advantage in this group. Of the five non-chemotherapy regimens, pembrolizumab was not as effective in combination with chemotherapy, but the benefit of this regimen was greater than pembrolizumab monotherapy and nivolumab monotherapy in terms of PFS.Conclusion In terms of efficacy, the best immunotherapy regimen for patients with KRAS-mutated NSCLC is the use of pembrolizumab monotherapy, which is also the best treatment for first-line therapy in this group, followed by the recommendation of nivolumab monotherapy, which is also the best treatment for second-line therapy in this group.