Rational application of the first‐line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta‐analysis

Abstract

Objective To compare the relative efficacy of immune checkpoint inhibitors (ICIs) or chemotherapy (CT) alone, or their combination modality in the first‐line treatment of advanced nonsmall cell lung cancer (NSCLC). Methods This meta‐analysis was performed on the eligible randomized controlled trials (RCTs) after searching web databases and meeting abstracts. The main research endpoints were the comparisons of median overall survival (mOS), the OS rate of 6 months (OSR6m), 1 year (OSR1y) and 2 years (OSR2y), median progression‐free survival (mPFS), the PFS rate of 6 months (PFSR6m) and 1‐year (PFSR1y), objective response rates (ORR), and treatment‐related adverse events (TRAEs). Results Eleven RCTs comprising 6278 cases were included. In the subgroup of programmed death‐ligand 1 (PD‐L1) ≥50%, compared with chemotherapy, the ICIs showed similar OSR6m ( P > 0.05), but significantly improved efficacy in mOS, OSR1y, OSR2y, and ORR (all P < 0.05), also had less grade ≥ 3 TRAEs. Compared with pembrolizumab alone, pembrolizumab plus CT in the subgroup of PD‐L1 ≥ 50% had similar mOS, OSR6m, OSR1y, and PFSR1y (all P > 0.05), but significantly improved mPFS, PFSR6m, and ORR (all P < 0.05 for interaction). Compared with the CT group, ICIs plus CT group with PD‐L1 ≥ 50% or <1% showed significant benefit in OS, PFS, and ORR (all P < 0.05). However, in the ICIs plus CT group with 1% ≤ PD‐L1 ≤ 49%, only PFS and ORR showed significant benefit compared with CT group (all P < 0.05), but not for results of OS. Conclusions The findings support the rationale for using pembrolizumab alone in the first‐line treatment of PD‐L1 ≥ 50% advanced NSCLC due to the similar OS and lower grade ≥ 3 TRAEs. However, the combination of ICIs and chemotherapy is strongly recommended in patients with PD‐L1 ≤ 49% for significant survival benefit.

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

“…Chemotherapy combined with immunotherapy has become the current standard care for patients with negative oncogenic drivers regardless of squamous or non-squamous NSCLC or programmed death ligand 1 (PD-L1) expression level [ 18 ]. However, chemotherapy plus bevacizumab is still an important first-line treatment option for patients with oncogenic driver negative NS-NSCLC who cannot tolerate immunotherapy, and is also a subsequent treatment for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy.…”

Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis

“…Several meta-analysis [9,10] have directly compared the response of platinum-based chemotherapy regimens and most of them found negative results for advanced NSCLC. The response and long-term prognosis of the above regimens are similar.…”

“…Several meta-analyses have directly compared the response of platinum-based chemotherapy regimens, and most of them found negative results for advanced NSCLC [9,10]. However, not all the chemotherapy regimens were directly compared by prospective randomized controlled trials or meta-analysis.…”

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

“…Chemotherapy combined with immunotherapy has become the current standard care for patients with negative oncogenic drivers regardless of squamous or non-squamous NSCLC or PD-L1 expression level [18]. However, some studies show that chemotherapy combined with the immunotherapy used in KEYNOTE-189 or IMpower150 trial is not cost effective [19,20].…”

“…However, some studies show that chemotherapy combined with the immunotherapy used in KEYNOTE-189 or IMpower150 trial is not cost effective [19,20]. Several meta-analyses demonstrated that immunotherapy combined with chemotherapy led to more toxicities as grade ≥ 3 TRAEs and more discontinuation of treatment than chemotherapy alone [18,21]. In fact, chemotherapy plus bevacizumab is still an important rst-line treatment option for patients with oncogenic driver negative NS-NSCLC who cannot tolerate immunotherapy, and is also a subsequent treatment for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy.…”