MET exon 14 skipping in NSCLC: An unMET Indian need.

Abstract

e13537 Background: The approval of capmatinib and tepotinib, selective MET tyrosine kinase inhibitors (TKI), has further shifted the therapeutic paradigm of advanced NSCLC. MET exon 14 skipping (MET ex14) alteration is a complex mechanism, reported in ~3-4% cases of NSCLC. Controlled trials have reported remarkable outcomes of selective MET TKIs, however real world outcomes from this part of the world are currently lacking. Methods: This is a non-interventional study reporting real world outcomes of NSCLC with MET ex14 from two apex cancer centers of India. 49 eligible patients were recovered from the electronic medical record archives. All cases with MET ex14 were included irrespective of clinicopathologic characteristics and therapy offered. Statistical analysis was performed using R studio. Results: Clinical characteristics are shown (Table). Treatment patterns were heterogeneous across therapy lines and included chemotherapy, MET TKIs and immune checkpoint inhibitors. 42/49 patients opted for treatment; rest dropped out owing to economic restraints. 1st line TKI was offered to 14 patients, and chemotherapy to 28 patients. 1st line PFS of TKI treated was 11.9 months (95%CI:5.8-17.8) vs. 5.9months (95%CI: 3.9-16.8) (p<0.002*) for the chemotherapy treated cases (HR for TKI: 0.3295 (95%CI: 0.1630 to 0.6663). Presence of TP53 co-mutation and male gender and were factors affecting 1st line PFS (p<0.06) on multivariate analysis. 2nd line treatment was opted by 13/14 patients in TKI treated group of which 5 received sequential TKI, and 8 received chemotherapy and 22/28 in chemotherapy treated group (TKI: 14, chemotherapy: 8). PFS for 2nd line TKI was 7.7 months (95%CI: 2.8-14.8) vs 4.6 months (95%CI:2.1-9.8) for chemotherapy {HR for TKI: 0.3641 (95%CI: 0.1378 to 0.9616)} (p<0.04*). The dropout rate from 1st to 2nd line was 36% and 44% in subsequent line. 28 (57%) received MET TKI at any given point in disease course. Median OS for patients treated with 1st line TKI was not reached at study end (95%CI: 9.2-NR) and was 20.7 months (95%CI:18.1-36.1) for chemotherapy (p=0.3). One year and 2 year survival rates for 1st line TKI and Chemotherapy were 86%vs 73% and 47% vs 45%, respectively. Conclusions: This is the largest cohort from India reporting real world uptake of TKI therapy in MET ex14 altered NSCLC. There is a blaring disparity with respect to accessibility of drugs, as well as prevailing socioeconomic restraints. This study clearly depicts an unmet need for more global clinical trials for rare genomic alterations as well as patient access programs in this part of the world. [Table: see text]