The addition of bevacizumab to TAS-102 (trifluridine/tipiracil; Lonsurf) reduced the risk of disease progression or death compared with TAS-102 alone in patients with chemorefractory metastatic colorectal cancer.
The addition of bevacizumab (Avastin) to TAS-102 (trifluridine/tipiracil; Lonsurf) reduced the risk of disease progression or death by 55% compared with TAS-102 alone in patients with chemorefractory metastatic colorectal cancer (mCRC), according to findings from an investigator-initiated, open-label, randomized phase II trial published in The Lancet Oncology.
At a median follow-up of 10 months (IQR, 6.8-14.0), the median progression-free survival (PFS) was 4.6 months with the combination compared with 2.6 months (95% CI, 1.6-3.5) with TAS-102 alone (HR, 0.45; 95% CI, 0.29-0.72; P = .0015).
“The combination of TAS-102 plus bevacizumab could be a new treatment option for patients with refractory metastatic colorectal cancer and could be a practice-changing development,” first author Per Pfeiffer, MD, PhD, Department of Oncology, Odense University Hospital, Odense 5000, Denmark, and coinvestigators wrote.
Between August 24, 2017, and October 31, 2018, the study accrued 93 patients with histopathologically confirmed mCRC refractory or intolerant to a fluoropyrimidine, irinotecan, oxaliplatin, and cetuximab or panitumumab (only for RAS wild-type). Prior bevacizumab, aflibercept, ramucirumab, or regorafenib was allowed. Patients had a WHO performance status of 0 or 1.
TAS-102 was administered at 35 mg/m² twice daily on days 1 to 5 and 8 to 12 every 28 days, and bevacizumab was administered at 5 mg/kg on days 1 and 15. The data cutoff date for this analysis was February 15, 2019. Investigator-evaluated PFS was the primary endpoint.
The disease control rate was 67% in the combination arm compared with 51% in the control arm (P = .14). The median overall survival was 9.4 months (95% CI, 7.6-10.7) versus 6.7 months (95% CI, 4.9-7.6), respectively (HR, 0.55; 95% CI 0.32-0.94; P = .028).
The investigators considered the toxicity to be tolerable. Neutropenia was the most common grade ≥3 adverse event (AE), occurring in 67% of the combination arm compared with 38% of the TAS-102 monotherapy arm. Serious AEs occurred in 41% of the TAS-102 plus bevacizumab group compared with 45% of the control arm. There were no treatment-related deaths.
“This trial supports the promising preclinical and phase 1/2 data for TAS-102 and shows that bevacizumab might be an excellent partner for TAS-102 in patients with chemorefractory metastatic colorectal cancer both in terms of activity and safety. We will continue to search for prognostic and predictive markers using the blood samples collected in this study,” wrote Pfeiffer et al. “Ongoing clinical trials are investigating this combination in earlier treatment lines for patients with metastatic colorectal cancer.”
TAS-102 is approved by the FDA for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an
anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
Avastin has 2 approved indications in this disease: mCRC, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment; and mCRC, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine/oxaliplatin-based chemotherapy for
second-line treatment in patients who have progressed on a first-line bevacizumab-containing regimen.
Pfeiffer P, Yilmaz M, Möller S, et al. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial. Lancet Oncol. 2020;21(3):412-420. doi: 10.1016/S1470-2045(19)30827-7.