A second phase 3 trial (ClinicalTrials.gov Identifier: NCT01244191) evaluated the non-selective TKI, tivantinib, in combination with erlotinib compared with erlotinib alone in patients with locally advanced or metastatic non-squamous NSCLC. Again, the trial was discontinued at interim analysis when there was no reasonable prospect of an improvement in overall survival.
Dr Boumber pointed out, however, that both of these trials did not select patients based on EGFR status. Newer studies of novel selective c-MET inhibitors in EGFR-mutant NSCLC have encouraging data, he added.
At the 18th Annual World Conference on Lung Cancer, 2 studies were presented on the MET TKI, savolitinib.
In the TATTON phase 1b expansion cohort, savolitinib plus osimertinib — used in patients with T790M-positive NSCLC — was assessed in patients with EGFR-mutant disease and MET-positive acquired resistance to first-line, first- and second-generation EGFR TKIs. Among patients who progressed after prior treatment with a first- or second-generation EGFR TKI, 53% of those with T790M-negative disease had a partial response, and 57% of those with T790M-positive disease had a partial response.1
Another phase 1b trial evaluated savolitinib plus gefitinib in patients with EGFR-mutant, MET-amplified advanced NSCLC that progressed on prior EGFR TKI–therapy. About one-third (31%) of patients had a partial response.2
“Based on these early data, I foresee a combination of an EGFR inhibitor with a c-MET inhibitor emerging as a new treatment option in the next 2 or 3 years,” said Dr Boumber.
- Ahn MJ, Han JY, Sequist LV, et al. TATTON ph Ib expansion cohort: osimertinib plus savolitinib for pts with EGFR-mutant MET-amplified NSCLC after progression on prior EGFR-TKI. Presented at: International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer; Yokohama, Japan: October 15-18, 2017. Abstract OA 09.03.
- Yang JJ, Fang J, Shu Y, et al. A phase Ib trial of savolitinib plus gefitinib for patients with EGFR-mutant MET-amplified advanced NSCLC. Presented at: International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer; Yokohama, Japan: October 15-18, 2017. Abstract OA 09.06.