Third-generation EGFR-TKIs linked to longer PFS in Chinese NSCLC cohort

A retrospective real-world study in China compared first- or second-generation EGFR-TKI combinations with third-generation EGFR-TKI monotherapy in 364 matched patients with untreated advanced EGFR-mutant NSCLC. Third-generation monotherapy was associated with longer progression-free survival, but overall survival did not differ significantly.

Matched cohort included 364 patients with untreated stage III/IV disease.
Median PFS was 20.5 versus 16.0 months.
Overall survival did not differ significantly between treatment groups.
Combination therapy had more adverse-event-related discontinuations and dose reductions.

This retrospective study included previously untreated patients with stage III or IV EGFR-mutant non-small cell lung cancer treated in China from 2017 to 2023. After propensity-score matching, 364 patients were compared: 1G/2G EGFR-TKI combination therapy versus 3G EGFR-TKI monotherapy. Progression-free survival (PFS) was the primary endpoint; overall survival (OS), response rate and disease control were secondary endpoints.

Median PFS was 20.5 months with 3G monotherapy and 16.0 months with combination therapy (hazard ratio, 0.63; 95% CI, 0.50–0.80; P<0.001). Median OS was 46.1 versus 41.6 months, respectively, with no statistically significant difference (HR, 0.95; 95% CI, 0.72–1.26; P=0.721). Response and disease-control rates were also similar. Adverse-event-related discontinuations and dose reductions were more frequent in the combination group.

The findings support longer PFS with 3G monotherapy, while not establishing an OS advantage. The authors note that subsequent use of 3G TKIs after progression may have contributed to the similar OS. Because this was a retrospective, nonrandomized study, residual confounding is possible; results do not establish equivalence between strategies. The authors describe 1G/2G combinations as a possible alternative where access to 3G TKIs is limited.

In practice

For clinicians treating previously untreated stage III/IV EGFR-mutant NSCLC, this Chinese real-world cohort found longer PFS with 3G EGFR-TKI monotherapy than with 1G/2G TKI combinations. It did not find a statistically significant OS difference, and response rates were similar; adverse-event-related discontinuation and dose reduction were more frequent with combination therapy. These retrospective, propensity-matched results support the authors’ preference for 3G therapy when accessible, but do not prove causality or establish that the strategies are equivalent in OS.

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Source

BMC Medicine: Comparative effectiveness of first-/second-generation EGFR-TKI combination therapy versus third-generation EGFR-TKI monotherapy in untreated locally advanced or metastatic EGFR-mutant NSCLC: a real-world, retrospective study in China ↗

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