Rebiopsy Feasibility and Clinical Impact on Metastatic Non-Small-Cell Lung Cancer With EGFR/ALK/ROS Oncogenic Driver Progression After Optimal Targeted Therapy: A Multicenter Real-World Analysis.

BACKGROUND: For metastatic non-small-cell lung cancer (mNSCLC) patients with oncogenic driver progression after tyrosine kinase inhibitors (TKIs), obtaining a new mutational profile is recommended to assess the mechanism of resistance. The feasibility of that recommendation and its clinical impact remain poorly studied.

METHODS: mNSCLC patients with EGFR mutation and ALK or ROS translocation progressing on optimal TKI therapy were screened for inclusion in an immunochemotherapy trial not requiring a new molecular profile determination. This analysis evaluated the rebiopsy rate and its clinical impact.

RESULTS: Among 148 patients, 79 (53.4%) analyzable re-biopsies showed 72/132 (54.6%) with EGFR mutations, 7/13 (53.8%) had ALK translocations and no (0/5) ROS translocations. Seventy-nine re-biopsies were tissue (37, 46.8%), liquid (26, 32.9%) or both samples (16, 20.3%). For patients harboring EGFR mutations, the rebiopsy was not contributive for 12/72 (16.7%), the initial mutation was not found for 9/72 (12.5%) and only the unchanged initial profile was detected for 22/72 (30.6%); new information was provided for 29/72 (40.3%). Among patients with ALK-translocated mNSCLCs, re-biopsies enabled identification of resistance mechanisms for 20%. Overall survival did not differ between patients with rebiopsy and those without.

CONCLUSIONS: In this population of patients with oncogenic driver progression under optimal targeted TKIs and in sufficiently good general condition to be included in an immunochemotherapy trial, only half were re-biopsied. Rebiopsy does not seem to improve the outcomes of these patients.