AI Article Synopsis
- The study investigates the effectiveness of chemotherapy (CHT) and immunotherapy (IO) in treating non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METΔ14ex), involving 110 patients over six years in Germany.
- Results indicate that combined CHT-IO treatment leads to better progression-free survival (PFS) and objective response rates compared to CHT alone, although overall survival (OS) was similar between CHT-IO and IO monotherapy.
- Additionally, patients with TP53 mutations showed improved outcomes with treatment, while never-smokers were at a greater risk for primary progressive disease with IO.
Article Abstract
Background: The efficacy of checkpoint inhibitors for non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METΔ14ex) remains controversial.
Materials And Methods: 110 consecutive METΔ14ex NSCLC patients receiving first-line chemotherapy (CHT) and/or immunotherapy (IO) in 10 German centers between 2016-2022 were analyzed.
Results: Combined CHT-IO was given to 35/110 (32%) patients, IO alone to 43/110 (39%), and CHT to 32/110 (29%) upfront. Compared to CHT, CHT-IO showed longer progression-free survival (median PFS 6 vs. 2.5 months, p = 0.004), more objective responses (ORR 49% vs. 28%, p = 0.086) and numerically longer overall survival (OS 16 vs. 10 months, p = 0.240). For IO monotherapy, OS (14 vs. 16 months) and duration of response (26 vs. 22 months) were comparable to those of CHT-IO. Primary progressive disease (PD) was more frequent with IO compared to CHT-IO (13/43 vs. 3/35, p = 0.018), particularly for never-smokers (p = 0.041). Higher PD-L1 TPS were not associated with better IO outcomes, but TP53 mutated tumors showed numerically improved ORR (56% vs. 32%, p = 0.088) and PFS (6 vs. 3 months, p = 0.160), as well as longer OS in multivariable analysis (HR=0.54, p = 0.034) compared to their wild-type counterparts. Any second-line treatment was administered to 35/75 (47%) patients, with longer survival for capmatinib or tepotinib compared to crizotinib (PFS 10 vs. 3 months, p = 0.013; OS 16 vs. 13 months, p = 0.270).
Conclusion: CHT-IO is superior to CHT, and IO alone also effective for METΔ14ex NSCLC, especially in the presence of TP53 mutations and independent of PD-L1 expression, but never-smokers are at higher risk of primary PD.
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| http://dx.doi.org/10.1016/j.ejca.2024.113556 | DOI Listing |
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