Dr Andre on the SOLSTICE Trial in mCRC

Thierry Andre, MD, professor of medical oncology, University Pierre et Marie Curie, head, Medical Oncology Department, St. Antoine Hospital, Paris, discusses the efficacy of trifluridine/tipiracil (TAS-102; Lonsurf) plus bevacizumab (Avastin) in patients with metastatic colorectal cancer (mCRC) and the safety profiles of the 2 arms of the phase 3 SOLSTICE trial (NCT03869892).

Dr Andre on Efficacy With TAS-102 Plus Bevacizumab in mCRC

The SOLSTICE trial evaluated the efficacy and safety of TAS-102 in combination with bevacizumab vs bevacizumab in combination with capecitabine (Xeloda) in treatment-naïve patients with unresectable mCRC who were unfit for intensive chemotherapy. In this trial, patients in the TAS-102 arm achieved a median progression-free survival (PFS) of 9.4 months (95% CI, 9.1-10.9) vs 9.3 months (95% CI, 8.9-9.8) in those in the capecitabine arm, missing the trial’s primary end point (HR, 0.87; 95% CI, 0.75-1.02). Overall survival (OS), the trial’s key secondary end point, was also not met. The median OS was 19.74 months (95% CI, 18.04-22.40) in the TAS-102 arm vs 18.59 months (95% CI, 16.82-21.39) in the capecitabine arm (HR, 1.06; 95% CI, 0.90-1.25).

Conversely, the phase 3 SUNLIGHT trial (NCT04737187), which investigated TAS-102 plus bevacizumab vs TAS-102 alone in patients with pretreated mCRC, demonstrated positive results with the TAS-102 combination in the third-line setting. In this trial, patients in the bevacizumab arm achieved a median OS of 10.8 months compared with 7.5 months in those in the TAS-102 monotherapy arm (HR, 0.61; 95% CI, 0.49-0.77; P < .001). In addition, the median PFS was 5.6 months with the combination vs 2.4 months with the monotherapy (HR, 0.44; 95% CI, 0.36-0.54; P < .001).

The findings from SUNLIGHT and SOLSTICE indicate that although TAS-102 plus bevacizumab should be the third-line standard of care in mCRC, this regimen was not superior to capecitabine plus bevacizumab in the first-line mCRC setting, and therefore should not be used as a first-line regimen, Andre says.

Dr Andre on the Safety Profiles of TAS-102 Plus Bevacizumab and Capecitabine Plus Bevacizumab in mCRC

In the SOLSTICE trial, the most common toxicities in the TAS-102 and capecitabine arms, respectively, were neutropenia (54% vs 1%) and hand-foot syndrome (0% vs 15%), Andre explains. The toxicity profiles may differ between the 2 arms because of differences in the bevacizumab dosing schedule, Andre notes. In the TAS-102 arm, patients received TAS-102 at 35 mg/m² twice daily on days 1 through 5 and 8 through 12 plus bevacizumab at 5 mg/kg on days 1 and 15 of each 28-day cycle. In the capecitabine arm, patients received capecitabine at 1000 mg/m² or 1250 mg/m² twice daily on days 1 through 14 plus bevacizumab at 7.5 mg/kg on day 1 of each 21-day cycle.