Network meta-analysis identifies best clinical choices for EGFR-mutated NSCLC
medwireNews: Osimertinib and gefitinib plus pemetrexed-based chemotherapy offer the best survival outcomes for patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC) compared with other first-line treatments, shows a network meta-analysis of randomized trials.
The study, conducted by Jianxing He (First Affiliated Hospital of Guangzhou Medical University, China) and colleagues, found that the longest progression-free survival (PFS) was achieved with osimertinib for patients with the exon 19 deletion and with gefitinib plus pemetrexed-based chemotherapy for those with Leu858Arg mutations.
Writing in The BMJ, the authors say their results provide “clinicians a reference source to evaluate strengths and weaknesses for practice choice among multiple promising options.”
The systematic review and network meta-analysis, which the researchers explain synthesizes evidence from direct and indirect comparisons, included 18 randomized controlled trials involving 4628 patients who received at least one of 12 treatments that fell into four categories:
- EGFR–tyrosine kinase inhibitors (TKIs);
- pemetrexed-based chemotherapy;
- pemetrexed-free chemotherapy; and
- combination treatments.
Of the treatments included, osimertinib offered the greatest PFS benefit, with significant differences versus dacomitinib (hazard ratio [HR] for progression or death=0.74), afatinib (HR=0.52), erlotinib (HR=0.48), gefitinib (HR=0.44), icotinib (HR=0.39), pemetrexed-based chemotherapy (HR=0.24), pemetrexed-free chemotherapy (HR=0.16), afatinib plus cetuximab (HR=0.44), and gefitinib plus pemetrexed (HR=0.65).
The team observed similar results with gefitinib plus pemetrexed-based chemotherapy, and there was no significant difference in PFS among patients treated with this combination compared with osimertinib.
For overall survival (OS), osimertinib and gefitinib plus pemetrexed-based chemotherapy were again found to offer the greatest benefit, with significantly better results compared with chemotherapy as well as the majority of EGFR–TKI monotherapies.
Subgroup analysis by EGFR mutation type showed that patients with an exon 19 deletion had the best PFS when treated with osimertinib relative to the other treatments, while those with the Leu858Arg mutation had the lowest risk for disease progression or death when receiving gefitinib plus pemetrexed based chemotherapy.
Afatinib appeared to be the best option for OS among patients with an exon 19 deletion, whereas there were no significant OS differences among the treatments for carriers of the Leu858Arg mutation.
The analysis also showed that different treatments had distinct toxicity profiles, and patients who received combination treatments were at greatest risk for grade 3 or higher adverse events, particularly those who received erlotinib plus bevacizumab. The lowest risk for adverse events was observed with icotinib.
He et al conclude that their findings “could complement current standard of care and enhance future trial design for advanced EGFR mutated NSCLC.”
By Laura Cowen
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