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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Exploring practical experience with different treatments in NSCLC patients with MET-deregulated: a retrospective
Mengmeng Li1, Jiuyan Huang1, Ruyue Xing2
1Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, 127 Dong Ming Road, Zhengzhou, 450008, China.
Background:
Mesenchymal to epithelial transition factor (MET) dysregulation in non-small-cell-lung-cancer (NSCLC) is understudied, with scant data on treatment outcomes.
Methods:
We retrospectively examined 160 NSCLC patients: 125 with primary MET mutations (further classified into MET exon 14 (METex14) skipping mutations and primary MET amplifications) and 35 with secondary MET amplifications. Patients underwent varied treatments: Chemotherapy, Immune monotherapy, Crizotinib, or Savolitinib. Secondary MET amplification patients were grouped by treatment: Group A (Class Ib MET-TKI with third-generation EGFR-TKI), Group B (Crizotinib with first-generation EGFR-TKI), and Group C (Crizotinib alone). One hundred and thirty patients have completed the whole treatment process. Their data were included in the study's survival analysis (included 95 patients with primary MET mutations and 35 patients with secondary MET amplifications).
Results:
Among METex14 skipping mutations patients (n = 57), median progression free survival (PFS) was: Chemotherapy 7.64 m, Crizotinib 8.5 m, Savolitinib 9.3 m, and Immunotherapy 3.87 m. Targeted therapies and chemotherapy significantly outperformed Immunotherapy. Sub-group analysis indicated splice donor region mutations benefited more than those at the polypyrimidine tract (9.23 m vs. 4.03 m, P = 0.038). For primary MET amplifications (n = 38), PFS was: Chemotherapy 2.84 m, Crizotinib 3.80 m, Savolitinib 5.23 m, and Immunotherapy 3.30 m. Patients with copy number (CN) > 5 had longer PFS than CN ≤ 5 (5.17 m vs. 3.44 m, P = 0.039). In secondary MET amplifications (n = 35), Group A and B had similar PFS (6.77 m and 6.57 m) versus Group C (3.13 m). Dual-target therapy PFS showed no difference between CN ≤ 5 and CN > 5 (8.63 m vs. 6.27 m, P = 0.29).
Conclusion:
NSCLC patients with METex14 skipping mutations benefit more from targeted therapies, especially those with splice donor mutations. MET amplification patients benefit universally from targeted therapies; primary MET amplifications show higher benefits with increased copy numbers. For secondary MET amplifications post-EGFR-TKI resistance, dual-target therapy surpasses Crizotinib monotherapy, independent of MET copy number.
Insights
Mesenchymal to epithelial transition factor (MET) targeted therapies improve outcomes for non-small-cell lung cancer (NSCLC) patients with METex14 skipping mutations, particularly those with splice donor mutations. Dual-target therapy is superior to monotherapy for secondary MET amplifications post-EGFR-TKI resistance.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Mesenchymal to epithelial transition factor (MET) dysregulation is understudied in non-small-cell lung cancer (NSCLC).
- Limited data exists on treatment outcomes for NSCLC patients with MET alterations.
Purpose of the Study:
- To investigate treatment outcomes in NSCLC patients with METex14 skipping mutations and MET amplifications.
- To compare the efficacy of different therapies including chemotherapy, immunotherapy, Crizotinib, and Savolitinib.
Main Methods:
- Retrospective analysis of 160 NSCLC patients with primary or secondary MET alterations.
- Patients received varied treatments: chemotherapy, immunotherapy, Crizotinib, or Savolitinib.
- Survival analysis included 130 patients who completed treatment.
Main Results:
- For METex14 skipping mutations, targeted therapies (Savolitinib 9.3m, Crizotinib 8.5m) and chemotherapy (7.64m) outperformed immunotherapy (3.87m). Splice donor mutations showed better PFS (9.23m) than polypyrimidine tract mutations (4.03m).
- For primary MET amplifications, Savolitinib (5.23m) and Crizotinib (3.80m) showed longer PFS than chemotherapy (2.84m). Higher copy numbers (CN>5) correlated with longer PFS (5.17m vs 3.44m).
- For secondary MET amplifications, dual-target therapies (Group A & B: 6.77m & 6.57m) were superior to Crizotinib monotherapy (Group C: 3.13m), irrespective of copy number.
Conclusions:
- NSCLC patients with METex14 skipping mutations benefit most from targeted therapies, especially those with splice donor mutations.
- MET amplification patients universally benefit from targeted therapies, with higher copy numbers showing improved outcomes for primary amplifications.
- Dual-target therapy is more effective than Crizotinib monotherapy for secondary MET amplifications following EGFR-TKI resistance.
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