EGFR-mutant NSCLC progressing on first-line osimertinib: rebiopsy in real-world and impact of second-line therapies (the "Rebiopsy on Osi" study).

BACKGROUND

Although rebiopsy at progression on osimertinib is recommended for patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), its real-world impact on clinical outcomes remains unclear. Rebiopsy on Osi is a multicenter, retrospective study assessing rebiopsy patterns, resistance mechanisms, and their impact on second-line treatment choices and outcomes in routine clinical practice.

METHODS

A total of 457 patients with advanced NSCLC harboring a common EGFR mutation (exon 19 deletion or L858R) who progressed on first-line osimertinib were identified from the Italian ATLAS registry. Patients were stratified according to rebiopsy status (tissue and/or plasma-based next-generation sequencing) and receipt of biomarker-driven adaptive second-line therapy.

RESULTS

Rebiopsy was performed in 206 patients (45.1%), predominantly via tissue sampling (66.2%). A resistance mechanism was identified in 80 cases (38.8%), with higher detection rates with tissue rebiopsy (46.6%) than with liquid biopsy (13.5%). MET amplification/overexpression emerged as the most frequent actionable resistance mechanism. Among 239 patients treated with second-line therapy, 39 (16.3%) received adaptive treatment, including 29 of 39 patients (74.3%) with MET amplification/overexpression who were treated with a MET-TKI-based regimen. Median progression-free survival (PFS) and overall survival (OS) were longer with adaptive therapy (7.3 and 14.1 months) than with rebiopsy without treatment adaptation (6.5 and 12.2 months) or no rebiopsy (5.1 and 8.2 months).

CONCLUSION

In real-world practice, rebiopsy identifies a resistance mechanism in slightly more than one third of patients, with actionable MET amplification/overexpression accounting for approximately one fifth of cases. Biomarker-driven adaptive therapy may improve clinical outcomes, supporting the implementation of rebiopsy in routine practice.