First-Line Treatments for Advanced EGFR-Mutated NSCLC Compared

In patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), treatment with osimertinib and gefitinib plus pemetrexed-based chemotherapy was found to be superior to other first-line therapies, according to a systematic review and network meta-analysis published in the BMJ.

For this investigation, study authors searched various databases from inception through May 20, 2019 for randomized controlled trials that evaluated the safety and efficacy of first-line treatments in advanced EGFR mutated NSCLC. Studies that reported on progression-free survival, overall survival, objective response rate (ORR), and toxicity (≥ grade 3 adverse events) were included in the analysis.

The literature search yielded 18 trials (N=4628), in which 12 treatment regimens were evaluated. “Consistent with gefitinib plus pemetrexed-based chemotherapy (hazard ratio [HR] 0.95, [95% CI 0.72 to 1.24]), osimertinib showed the most favorable progression free survival, with significant differences versus dacomitinib (HR 0.74, [95% CI 0.55 to 1.00]), afatinib (HR 0.52, [95% CI 0.40 to 0.68]), erlotinib (HR 0.48, [95% CI 0.40 to 0.57]), gefitinib (HR 0.44, [95% CI 0.37 to 0.52]), icotinib (HR 0.39, [95% CI 0.24 to 0.62]), pemetrexed-based chemotherapy (HR 0.24, [95% CI 0.17 to 0.33]), pemetrexed-free chemotherapy (HR 0.16, [95% CI 0.13 to 0.20]), afatinib plus cetuximab (HR 0.44, [95% CI 0.28 to 0.71]), and gefitinib plus pemetrexed (HR 0.65, [95% CI 0.46 to 0.92]),” the authors reported. 

As for overall survival, osimertinib and gefitinib plus pemetrexed-based chemotherapy were found to provide the best benefit (HR 0.94, [95% CI 0.66 to 1.35]). Gefitinib plus pemetrexed-based chemotherapy was also observed to be the best at achieving objective response; no significant differences were noted with EGFR-tyrosine kinase inhibitor monotherapies, however ORR was significantly better with these agents than with chemotherapy.

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In a subgroup analysis by EGFR mutation type, the authors found that treatment with osimertinib provided the best progression-free survival in patients with the exon 19 deletion. In patients with Leu858Arg mutations, gefitinib plus pemetrexed-based chemotherapy was observed to be superior.

With regard to safety, there was an increased likelihood of ≥ grade 3 adverse events with erlotinib plus bevacizumab; in general, combination therapies were associated with increased toxicity. Among all the agents, icotinib and osimertinib treatment resulted in the fewest serious adverse events.

Based on their findings, the authors concluded that “osimertinib and gefitinib plus pemetrexed based chemotherapy were shown to be similar to the optimal treatments for patients with EGFR mutated NSCLC, and were preferentially recommended to patients with exon 19 deletion or Leu858Arg, respectively.” 

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