The efficacy and safety of combination therapy with immune checkpoint inhibitors in non-small cell lung cancer: A meta-analysis.

PURPOSE

Combination therapies with immune checkpoint blockade demonstrate promising antitumor activity and safety in Non-small Cell Lung Cancer (NSCLC). However, whether the combination therapy is superior to their monotherapies, and which combination regimen is most efficacious remain unknown. This meta-analysis aims to synthesize the current available evidences on the efficacy and safety of combination immunotherapy in patients with NSCLC.

METHODS

PubMed, Embase and Cochrane Library were searched. Randomized controlled trials (RCTs) investigating combination therapy with immune checkpoint inhibitors in NSCLC were included.

RESULTS

We identified nine RCTs including a total of 5,142 patients. The study showed that the pooled hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) for combination therapy were 0.74 (95% CI: 0.63-0.86, p = 0.001) and 0.65 (95% CI: 0.56-0.73, p = 0.004); the pooled odds ratios (ORs) of objective response rates (ORRs) and grade 3 or higher adverse events (AEs) were 1.51 (95% CI: 1.02-1.99, p < 0.001) and 1.30 (95% CI: 1.03-1.57, p = 0.007). Subgroup analysis showed that the OR of grade 3 or higher AEs for immunotherapy plus chemotherapy was higher than that of chemotherapy alone, but did not reach statistical significance (p = 0.061) , and there was PFS and OS benefit for either immunotherapy plus chemotherapy, double agent immunotherapy or immunotherapy plus targeted plus chemotherapy combination regimens.

CONCLUSIONS

Combination therapy with immune checkpoint inhibitors showed more clinical benefit for patients with NSCLC, with increased grade 3 or higher AEs, but toxicities were manageable.