269P - MET alterations in EGFR mutated NSCLC: A lesser known evil

Background

Latest NCCN/ASCO/CAP guidelines recommend panel based molecular testing in all cases of NSCLC, in view of FDA approvals for 7 biomarkers driven processes. In EGFR mutated NSCLC, approximately 10% TKI treated patients present with upfront progressive disease owing to intrinsic resistance mechanisms. MET gene alterations involving amplification and exon 14 skipping mutation are among these, the latter being mutually exclusive. MET amplification has been reported both as a primary and as an acquired resistance mechanism in EGFR mutated NSCLC. However, real world data describing the same is currently sparse. This study highlighted the frequency of the same in an Indian EGFR mutated NSCLC cohort.

Methods

100 patients of EGFR mutated advanced NSCLC treated with EGFR TKI were tested for MET alterations using the custom panel. 70 good responders and 30 non-responders were recruited. NGS was performed on diagnostic tumor blocks, and MET FISH for CEP7 ratio was done on both diagnostic and metastatic tumor blocks. Clinical features and survival outcomes were collated and analyzed.

Results

30 patients (non-responders) who developed progression upfront, showed MET amplification in 3 (10%) cases, with the copy number being 12, 14.5 and 21 respectively. The PFS of these patients to EGFR TKI were 7.9. 3.5, and 6 months respectively. Among the good responders (n=70), 18 (25.7%) cases developed MET amplification as a secondary resistance mechanism. No relation to age, gender, smoking of EGFR mutation subtype were noted in these cases. The response rate in EGFR+/MET+ was 62.7% vs. 79.6% in EGFR+/MET- group (p<0.03). The median PFS was 11.8 months overall, and for the EGFR+/MET- it was 10.7 months vs. 9.8 months in EGFR+/MET+ group. The median OS however was not reached for the cohort.

Conclusions

This initial pilot study highlights that analogous to ethnic differences in EGFR and ALK in India, MET alterations may also occur at a high frequency, impacting TKI therapy. It is important to test for these alterations in a panel based NGS, in order to salvage tissue and avoid inadvertent delays through sequential single gene assays.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Ullas Batra.

Funding

Novartis Oncology.

Disclosure

All authors have declared no conflicts of interest.