CHICAGO – Oxaliplatin/5-fluorouracil is the new benchmark for previously treated advanced biliary tract cancers, though more research is needed to improve outcomes, an investigator said at the annual meeting of the American Society of Clinical Oncology.
Modified FOLFOX (mFOLFOX) added to active symptom control reduced risk of death by 31% versus active symptom control alone in patients who had progressed following standard cisplatin/gemcitabine chemotherapy, according to Angela Lamarca, MD, PhD, of the University of Manchester, England, who presented results in an oral presentation at the meeting.
While the chemotherapy did improve survival versus no chemotherapy, the overall benefit was modest and the toxicity was moderate, William P. Harris, MD, said in a discussion of the study results.
“At the moment, based on this study, I think that FOLFOX is the benchmark moving forward in the second-line setting, but certainly clinical trials are reasonable in this space,” said Dr. Harris, who is with the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.
Novel therapies seem particularly “appealing” in biliary tract cancers, he said, based on results so far from studies that include inhibitors targeting PD-1, FGFR1-3, and IDH1, among others.
The present study, known as ABC-06, was the first-ever prospective phase 3 trial to evaluate the benefit of additional chemotherapy after cisplatin/gemcitabine in patients biliary tract cancers, Dr. Lamarca said.
While cisplatin plus gemcitabine is established as first-line therapy for advanced biliary tract cancers, the role of second-line chemotherapy has been unclear, she said in her presentation.
In the trial initiated by Dr. Lamarca and colleagues, 162 patients were randomized to active symptom control alone, or active symptom control plus modified FOLFOX chemotherapy given every 14 days for up to 12 cycles.
The rate of grade 3-4 adverse events was 59% in the modified FOLFOX arm versus 40% in the active symptom control arm. There were three chemotherapy-related deaths, due respectively to renal failure, febrile neutropenia, and acute kidney injury, according to the report.
Grade 3-4 fatigue, infections, and decreased neutrophil count were more common in the chemotherapy arm, while anorexia and thromboembolic events were more often seen in the group of patients receiving active symptom control alone, Dr. Lamarca said.
The study’s primary endpoint of overall survival was met, with a hazard ratio of 0.69 (95% CI, 0.50-0.97; P = .031) favoring the chemotherapy arm after adjusting for platinum sensitivity, albumin, and stage.
The difference in median overall survival was “modest,” Dr. Lamarca said, at 6.2 months in the modified FOLFOX arm versus a higher-than-expected 5.3 months in the active symptom control arm (investigators had anticipated a median survival of 4 months).
However, “clinically meaningful” increases were seen with FOLFOX in both the 6-month overall survival rate, at 50.6% versus 35.5%, and the 12-month overall survival rate, at 25.9% versus 11.4% she said in her presentation.
“Modified FOLFOX chemotherapy combined with active symptom control should therefore become the standard of care in the second-line setting for patients with advanced biliary tract cancers,” she said.
Dr. Lamarca reported disclosures related to Eisai, Nutricia, Ipsen, Merck, Novartis, Pfizer, Abbott Nutrition, Advanced Accelerator Applications, Bayer, Celgene, Delcath Systems, Mylan, NanoString Technologies, and Sirtex Medical.
SOURCE: Lamarca A et al. ASCO 2019, Abstract 4003.