According to study results to be presented by Valle et al at the 2020 Gastrointestinal Cancers Symposium (Abstract 477), the addition of either ramucirumab or merestinib to the standard first-line therapy for biliary tract cancer—gemcitabine plus cisplatin—did not improve progression-free survival, overall survival, or objective response. However, the treatment was well tolerated.
Ramucirumab is a VEGF receptor-2 antagonist, and merestinib is an experimental drug in development that is a small molecule inhibitor of MET and several other receptor tyrosine kinases.
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Study Methodology
In the randomized, double-blind, phase II trial, 309 patients with biliary tract cancer were randomly assigned 2:1:2:1 to receive 80 mg of merestinib orally once a day, placebo orally once a day, 8 mg/kg of ramucirumab intravenously on days 1 and 8 of a 3-week cycle, or placebo intravenously on days 1 and 8 of a 3-week cycle. Patients also received up to eight cycles of intravenous gemcitabine at 1,000 mg/m2 plus cisplatin at 25 mg/m2 on days 1 and 8 of a 3-week cycle. Treatment with ramucirumab, merestinib, or placebo could continue until disease progression.
To be enrolled, patients had to have an ECOG performance status of 0 or 1 and measurable disease.
The primary endpoint of the trial was progression-free survival; overall survival, objective response rate, and safety were listed as secondary endpoints.
Findings
For the 106 patients treated with ramucirumab/gemcitabine/cisplatin, the median progression-free survival was 6.47 months (80% confidence interval [CI] = 5.65–7.13), the median overall survival was 10.45 months (95% CI = 8.48–11.76), and the objective response rate was 33% (95% CI = 31.1%, 22.3%–39.9%).
Among the 102 patients treated with merestinib/gemcitabine/cisplatin, the median progression-free survival was 6.97 months (80% CI = 6.21–7.13), the median overall survival was 14.03 months (95% CI = 11.96–16.36), and the objective response rate was 20% (95% CI = 19.6%, 11.9%–27.3%).
Finally, in patients dosed with placebo plus the standard of care, the median progression-free survival was 6.64 months (80% CI = 5.59–6.83), the median overall survival was 13.04 months (95% CI = 11.40–15.31), and the objective response rate was 33% (95% CI = 32.7%, 23.5%–41.8%).
Fewer patients treated with ramucirumab received postdiscontinuation systemic therapy than patients who were treated with merestinib or placebo. The most common grade ≥ 3 treatment-emergent adverse events in patients treated with ramucirumab were neutropenia, thrombocytopenia, and anemia; for patients treated with merestinib, they were neutropenia, thrombocytopenia, and increased alanine aminotransferase.
The study authors concluded, “Progression-free survival, overall survival, and objective response were not improved with the addition of ramucirumab or merestinib to gemcitabine/cisplatin. Treatment was well tolerated, with safety profiles consistent with known profiles for ramucirumab, merestinib, and gemcitabine/cisplatin. Translational studies are ongoing.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
