Clinical Trial of Frontline Trifluridine/Tipiracil Plus Bevacizumab Will Continue Despite Not Meeting Primary Objective Unresectable Metastatic CRC

Despite not meeting its primary end point of superior progression-free survival, the phase 3 SOLSTICE trial’s secondary end point analysis will continue in patients with unresectable metastatic colorectal cancer being treated with trifluridine/tipiracil and bevacizumab.

Although the phase 3 SOLSTICE trial (NCT03869892) examining the use of frontline trifluridine/tipiracil (TAS-102; Lonsurf) and bevacizumab (Avastin) in patients with unresectable metastatic colorectal cancer (mCRC) who are ineligible for intensive therapy did not meet its primary end point of progression-free survival (PFS) superiority versus bevacizumab plus capecitabine, the trial will continue to follow patients as planned.1

Since the regimen has not induced deleterious effects and no new safety issues have been observed in either study arm, investigators intend to conduct the study’s secondary end point analysis. Findings from the study will be presented at an upcoming medical event, according to the company responsible for developing TAS-102, Servier.

“We remain committed to improving outcomes in mCRC and we will continue to follow patients as planned in order to perform the main secondary end point analysis on overall survival in 2023,” Patrick Therasse, MD, PhD, head of late stage and life cycle management and deputy h ofead Oncology and Immuno-Oncology Therapeutic Area at Servier, said in a press release. “The clinical value of Lonsuf in its current indications remains unchanged, and the ongoing Phase III SUNLIGHT trial (LONSURF + bevacizumab versus LONSURF in 3rd line mCRC) is proceeding as planned [NCT4737187].”

The open-label, randomized SOLSTICE trial enrolled 856 patients with unresectable mCRC who either did not require or were not candidates for intensive therapy. Patients who enrolled were randomized 1:1 to be treated with either 35 mg/m2 of oral TAS-102 twice daily plus 5 mg/kg of intravenous bevacizumab every 2 weeks or 1250 mg/m2 of capecitabine orally on days 1 to 14 plus 7.5 mg/kg of bevacizumab.

The study’s primary end point was superior PFS with the experimental regimen vs the control group.

The regimen was previously assessed as part of the phase 2 TASCO1 trial (NCT02743221) in which TAS-102/bevacizumab resulted in promising overall survival (OS) in patients with unresectable mCRC.2 Findings from the study’s final analysis, which were presented the at the 2021 Gastrointestinal Cancer Symposium, highlighted a median OS of 22.31 months (95% CI, 18.00-23.69) in the experimental arm vs 17.67 months (95% CI, 12.58-19.81) among those treated with capecitabine and bevacizumab (HR, 0.78; 95% CI, 0.55-1.10).

Additional findings from the trial identified a median PFS of 9.2 months (95% CI, 7.59-11.56) and 7.8 months (95% CI, 5.55-10.15) in each arm, respectively. The 12-month PFS rates were 40% in the TAS-102 arm and 30% in the control arm.

“[Patients with] metastatic colorectal cancer who are not well enough to undergo intensive chemotherapy have limited options, and quality of life is a priority,” Professor Thierry André, MD, Saint Antoine Hospital, Paris, France, and lead investigator for the SOLSTICE study, concluded. “We are continuously searching for new ways to give these patients efficient treatment with low toxicities.”


  1. Servier announces outcome from the primary analysis of the Phase III SOLSTICE trial assessing LONSURF® (trifluridine/tipiracil) + bevacizumab in a 1st line setting for patients with unresectable mCRC non-eligible for intensive therapy. News release. Servier. October 22, 2021. Accessed October 22, 2021.
  2. Van Cutsem E, Danielewicz I, Saunders MP, et al. Phase II study evaluating trifluridine/tipiracil + bevacizumab and capecitabine + bevacizumab in first-line unresectable metastatic colorectal cancer (mCRC) patients who are noneligible for intensive therapy (TASCO1): Results of the final analysis on the overall survival. J Clin Oncol. 2021;39(suppl):14. doi:10.1200/JCO.2021.39.3_suppl.14