Real world experience with MET inhibitors in MET exon 14 skipping mutated non-small cell lung cancer: largest Indian perspective

A total of 49 patients harboring MET ex14 alterations were included in the current study. Table 1. shows the clinico-pathological features of these patients. Treatment patterns were heterogeneous across therapy lines and included systemic therapy, MET TKIs and immunotherapy. Approximately 85.71% (42/49) patients opted for treatment. First line TKIs were offered to 14 patients; while chemotherapy was given to 28 patients. First-line TKIs doubled the PFS in comparison to chemotherapy arm (mPFS: 11.9 months vs. 5.9 months, p < 0.002*, HR for TKI: 0.3295. On multivariate analysis, male sex and TP53 co-mutation were factors influencing the first-line PFS (p < 0.06). Second line treatment was taken by 13/14 patients in the TKI arm of which 5 received sequential TKI, while 8 received chemotherapy. Similarly, 22/28 patients in the chemotherapy arm received second line treatment. Of these 22 patients, 14 received sequential TKIs, while 8 received next line systemic chemotherapy (TKIs: 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 arm (HR for TKI: 0.3641, p < 0.04*). Around 57% (28/49) received MET TKI therapy at any given time point during the disease course. Median OS for patients treated with 1st line TKI and systemic chemotherapy was not reached (95% CI 9.2-NR months) and 20.7 months (95% CI 18.1-36.1 months) respectively at the study endpoint (p = 0.3). Table 1 Characteristics of the patients at baseline Clinicopathological Features n = 49 % Age (Years) Median: 70 (Range, 39-85) - ECOG PS 1 40 81.6 ≥2 9 18.4 Gender Male 33 67.3 Female 16 32.7 Smoking Status Ever smoker 34 69.3 Never smoker 15 30.7 Brain metastases Present at diagnosis 4 8.3 Developed Later 12 24.4 Absent 33 67.3 Histology Adenocarcinoma 33 67.3 Squamous cell carcinoma 8 16.3 Adenosquamous carcinoma 8 16.3 Co-mutations TP53 12 24.4 KRAS 1 2.1 CTNNB1 1 2.1 MET Copy number gain 1 2.1 None 34 69.3 PDL1 < 1% 9 18.4 1-49% 20 40.8 > 49% 20 40.8 MET exon 14 skipping DNA only 0 0 RNA only 30 61.2 Both DNA & RNA 19 38.8 CONCLUSION: The current study comprises of the largest MET ex14 mutated NSCLC patient cohort reporting on the real-world data of MET TKI therapy from the Indian subcontinent. MET TKI showed higher systemic and intracranial efficacy with manageable safety profile. The current study represents an unmet need for more clinical phase 3 study for rare genomic alterations as well as patient access programs in the Indian subcontinent.