Clinical lung cancer · 2026
MET Testing and Treatment Sequencing After Disease Progression on First-Line Osimertinib in Patients With EGFR-Mutated Advanced NSCLC and Acquired MET Overexpression and/or Amplification: A Global Real-World Study.
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Rotow Julia, Malapelle Umberto, Cuadras Daniel, Lara Núria, Caro Noelia, Roset Montserrat, Pedros Montse, Pinchevsky Yacob, Kim YongJin
Аннотация
BACKGROUND: Given the potential benefit of MET-tyrosine kinase inhibitors (TKIs) after progression on osimertinib in EGFR-mutated advanced NSCLC, evaluating real-world biomarker testing and treatment sequencing is important. We report findings from a global, direct-to-physician, survey-based chart review.
PATIENTS AND METHODS: Physicians treating NSCLC were surveyed regarding rebiopsy and MET testing practices and awareness of MET overexpression and/or amplification (OverExp/Amp) cutoff levels. Biomarker testing, MET OverExp/Amp quantification and treatment sequencing were assessed in patients with EGFR-mutated advanced NSCLC with acquired MET OverExp/Amp after progression on first-line osimertinib, who received second-line treatment between January 2018 and December 2023 (data cutoff: April 8, 2025).
RESULTS: Among 280 physicians, rebiopsy practices varied; the most commonly reported MET testing method was NGS (78%), followed by IHC (11%) and FISH (11%). Understanding of MET OverExp/Amp cutoff levels varied, with 35%-47% of physicians unaware of appropriate cutoffs. Among 367 patients (94% with MET Amp), MET alterations were mostly detected through tissue-based (58%) versus liquid-based tests (31%) or both (11%). MET alterations were detected using NGS (77%), then PCR (10%), IHC (10%), and FISH (4%). In 257 patients with MET cutoff data available, most MET Amp had gene copy numbers ≥6 (88%). MET-TKIs (29%) and EGFR-TKIs (24%) were the most common second-line treatments, followed by chemotherapy (20%). Of 193 patients with high MET levels, most received targeted treatments (MET-TKI 35%, EGFR-TKI 23%).
CONCLUSION: Rebiopsy practices and knowledge of MET OverExp/Amp cutoffs varied among physicians. IHC/FISH were underutilized; however, their use should be encouraged for optimal patient identification and treatment selection.
PATIENTS AND METHODS: Physicians treating NSCLC were surveyed regarding rebiopsy and MET testing practices and awareness of MET overexpression and/or amplification (OverExp/Amp) cutoff levels. Biomarker testing, MET OverExp/Amp quantification and treatment sequencing were assessed in patients with EGFR-mutated advanced NSCLC with acquired MET OverExp/Amp after progression on first-line osimertinib, who received second-line treatment between January 2018 and December 2023 (data cutoff: April 8, 2025).
RESULTS: Among 280 physicians, rebiopsy practices varied; the most commonly reported MET testing method was NGS (78%), followed by IHC (11%) and FISH (11%). Understanding of MET OverExp/Amp cutoff levels varied, with 35%-47% of physicians unaware of appropriate cutoffs. Among 367 patients (94% with MET Amp), MET alterations were mostly detected through tissue-based (58%) versus liquid-based tests (31%) or both (11%). MET alterations were detected using NGS (77%), then PCR (10%), IHC (10%), and FISH (4%). In 257 patients with MET cutoff data available, most MET Amp had gene copy numbers ≥6 (88%). MET-TKIs (29%) and EGFR-TKIs (24%) were the most common second-line treatments, followed by chemotherapy (20%). Of 193 patients with high MET levels, most received targeted treatments (MET-TKI 35%, EGFR-TKI 23%).
CONCLUSION: Rebiopsy practices and knowledge of MET OverExp/Amp cutoffs varied among physicians. IHC/FISH were underutilized; however, their use should be encouraged for optimal patient identification and treatment selection.