Crequit P, et al. - The comparative efficacy and tolerability of all second-line treatments for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR) are evaluated by a systematic review and network meta-analysis. Nivolumab, pembrolizumab, atezolizumab, and pemetrexed plus erlotinib may be the most effective second-line treatments for NSCLC in terms of OS. The four prescribed treatments appear to have relatively poor performance. However, the effect on life expectancy of immunotherapy versus other treatments ought to be further investigated by future examinations, and more trials comparing the novel treatments are required to decrease uncertainty in these outcomes.

Methods

• For this study, they conducted a systematic review and network meta-analysis.
• MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and the US Food and Drug Administration website, as well as other sources, were searched for available reports up to June 6, 2017.
• Two reviewers independently selected published and unpublished reports of RCTs comparing any second-line treatments, extracted information and evaluated the risk of bias of all included trials.
• A Bayesian network meta-analysis was performed in this study.
• The primary outcomes were overall survival (OS) and progression-free survival (PFS).
• Secondary outcomes included objective response (ObR), the number of serious adverse events, and quality of life.

Results

• Total one hundred two RCTs were selected for this study.
• This study involved 36,058 patients (62% male, median age 61 years, 81% with stage IV cancer, 80% smokers, and 92% with performance status 0-1).
• They uncovered a differential reporting of outcomes between effectiveness and safety outcomes.
• Fifty percent of the trials reported safety outcomes and under 20% quality of life.
• For OS, nivolumab was more effective than docetaxel (hazard ratio (HR) 0.69, 95% credible interval (CrI) 0.56-0.83), pemetrexed (0.67, 0.52-0.83), erlotinib (0.68, 0.53-0.86), and gefitinib (0.66, 0.53-0.83).
• Pembrolizumab, atezolizumab, and pemetrexed plus erlotinib were also significantly more effective than docetaxel, pemetrexed, erlotinib, and gefitinib.
• For PFS, erlotinib plus cabozantinib was more effective than docetaxel (HR 0.39, 95% CrI 0.18-0.84), pemetrexed (0.38, 0.18-0.82), erlotinib (0.37, 0.18-0.78), and gefitinib (0.38, 0.18-0.82).
• Cabozantinib and pemetrexed plus erlotinib were also significantly more effective than the four recommended treatments.
• For ObR, no treatment was significantly more effective.
• The effectiveness of the four suggested treatments was similar and they were ranked among the 25 less-effective treatments.
• For safety, evidence is insufficient to draw certain conclusions.