Subset of Lung Cancer Patients Have Improved Outcomes with Tivantinib, Erlotinib Combination

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Advanced lung cancer patients who have tumors with mutations in the epidermal growth factor receptor (EGFR) gene may benefit from the combination treatment of erlotinib standard therapy plus tivantinib.

The results of a preplanned subset analysis of a large phase III previously reported clinical trial were presented (abstract B194) at the International Conference on Molecular Targets and Cancer Therapeutics conference, held November 5-9, 2015, in Boston. This conference was organized by the American Association for Cancer Research and the National Cancer Institute.

The addition of tivantinib, an experimental, oral anticancer drug that has selective anti-c-Met activity, to the standard of care EGFR inhibitor ,erlotinib, improved progression-free survival (PFS), response rate, and also overall survival in some cases, compared to erlotinib alone in patients with previously treated, advanced, non-squamous, EGFR and MET inhibitor naive non-small cell lung cancer (NSCLC).

Previously published in the Journal of Clinical Oncology, results of the randomized phase III MARQUEE patient trial (1,048 enrolled) demonstrated that adding tivantinib to erlotinib treatment improved PFS, but did not improve overall survival compared to erlotinib alone in the overall study population. Patients in the erlotinib plus placebo arm had a median overall survival of 7.8 months compared to 8.5 months in the combination arm (P = .81).

Of the 109 patients on trial who had tumors positive for an EGFR mutation (56 assigned to the combination and 53 to the control arm), those treated with trivantinib had a median PFS of 13.0 months compared to 7.5 months in the control group (P = .0016).

Although not statistically significant, the overall response rate and median overall survival were also increased, from 43% to 61% and from 20.0 months to 25.5 months, respectively. According to Wallace Akerley, MD, director of thoracic oncology at the Huntsman Cancer Institute at the University of Utah in Salt Lake City, greater numbers of patients give a greater chance to show small differences, so this subset analysis was capable of showing only major differences in outcome. Overall survival was also improved from 20.0 months to 25.5 months in the experimental group, although the difference was not statistically significant (P = 0.1).

The most common adverse events occurring with erlotinib plus tivantinib versus erlotinib plus placebo were rash (33.1% vs 37.3%, respectively), diarrhea (34.6% vs 41.0%), asthenia or fatigue (43.5% vs 38.1%), and neutropenia (grade 3 to 4; 8.5% vs 0.8%).

At data cutoff, six patients of the 56 patients in the combination arm were still on therapy. The duration of therapy ranges from 16 to 25 months.

Because these results are part of a preplanned analysis, the results are not sufficient to demonstrate the efficacy of the combination compared to erlotinib alone. Further studies are needed to confirm these results.

The study was sponsored by ArQule and Daiichi Sankyo.