In a Danish phase II study reported in The Lancet Oncology, Per Pfeiffer, MD, PhD, and colleagues found that the addition of bevacizumab to trifluridine/tipiracil, also known as TAS-102, significantly improved progression-free survival among patients with chemorefractory metastatic colorectal cancer.
Per Pfeiffer, MD, PhD
In the open-label multicenter trial, 93 patients with colorectal cancer who were refractory to or intolerant of treatment with fluoropyrimidines, irinotecan, oxaliplatin, and cetuximab or panitumumab (only for RAS wild-type disease) were randomly assigned between August 2017 and October 2018 to receive oral trifluridine/tipiracil at 35 mg/m² twice daily on days 1 to 5 and 8 to 12 every 28 days alone (n = 47) or trifluridine/tipiracil plus bevacizumab at 5 mg/kg on days 1 and 15 (n = 46) until disease progression or unacceptable toxicity. Previous therapy with bevacizumab, aflibercept, ramucirumab, or regorafenib was permitted. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population.
On the clinical cut-off date in February 2019, median follow-up was 10.0 months. Median progression-free survival was 4.6 months in the combination group vs 2.6 months in the trifluridine/tipiracil group (hazard ratio [HR] = 0.45, P = .0015). The difference remained significant when analysis was adjusted for the stratification factors of study center and RAS mutation status (HR = 0.47, P = .0015).
Median overall survival was 9.4 months vs 6.7 months (HR = 0.55, P = .028; HR = 0.58, P = .048, after adjustment for stratification factors). Disease control rates (one partial response was observed in the combination group) were 67% vs 51% (P = .14).
The most common treatment-related grade ≥ 3 adverse event in the combination group was neutropenia (67% vs 38%); the most common treatment-related grade ≥ 3 nonhematologic adverse event was diarrhea (9% vs 0%). Serious adverse events occurred in 41% vs 45% of patients. No treatment-related deaths were observed.
The investigators concluded, “In patients with chemorefractory metastatic colorectal cancer, [trifluridine/tipiracil] plus bevacizumab, as compared with [trifluridine/tipiracil] monotherapy, was associated with a significant and clinically relevant improvement in progression-free survival with tolerable toxicity. The combination of [trifluridine/tipiracil] plus bevacizumab could be a new treatment option for patients with refractory metastatic colorectal cancer and could be a practice-changing development.”
Dr. Pfeiffer, of the Department of Oncology, Odense University Hospital, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Servier. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.