Clinical option of pemetrexed-based versus paclitaxel-based first-line chemotherapeutic regimens in combination with bevacizumab for advanced non-squamous non-small-cell lung cancer and optimal maintenance therapy: evidence from a meta-analysis of randomized control trials

摘要

In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy. All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP?±?B) and paclitaxel-carboplatin with bevacizumab (PC? ?B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem? ?B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events. Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP?±?B and PC? ?B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP?±?B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC? ?B (all P??0.05). PP?±?B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC? ?B (all P??0.001). The other three RCTs were included in an analysis that compared Pem? ?B and B as a maintenance treatment. Compared with B, Pem? ?B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P??0.001). Although the first-line PP? ?B regimen had longer PFS and PFSR1y than the PC? ?B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.