Eric Van Cutsem, MD, PhD
Patients with metastatic colorectal cancer (mCRC) who are not eligible for chemotherapy or surgical resection may have a new first-line treatment option, according to findings presented on June 22, 2018, at the 20th World Conference of Gastrointestinal Cancer. Treatment with trifluridine/tipiracil (Lonsurf) combined with bevacizumab (Avastin) improved progression-free survival (PFS) in thsese patients over comparator capecitabine plus bevacizumab.
The results of the TASCO1 clinical trial (NCT02743221) demonstrated a median PFS of 9.23 months (95% CI, 7.59-11.56) with trifluridine/tipiracil plus bevacizumab compared to 7.82 months (95% CI, 7.59-11.56) in patients receiving capecitabine plus bevacizumab (HR, 0.71; 95% CI, 0.48-1.06).
“This efficacy was observed across all stratification factors and most predefined subgroups,” said Eric Van Cutsem MD, PhD, professor of Internal Medicine at the University of Leuven and head of the Digestive Oncology Unit at the University Hospital Gasthuisberg in Leuven, Belgium. Van Cutsem presented the findings of this study on behalf of the TASCO1 trial investigators.
TASCO1 is a randomized, global, non-comparative phase II study evaluating the efficacy and safety of trifluridine/tipiracil plus bevacizumab compared to capecitabine plus bevacizumab in the first-line setting for treatment of patients with unresectable mCRC who were non-eligible for standard first-line therapy.
TASCO1 enrolled patients who were not eligible for standard chemotherapy or for curative resection according to the investigator’s judgment. Patients were randomized 1:1 and stratified by RAS mutation status, ECOG performance status, and country. They either received oral trifluridine/tipiracil at 35 mg/m2
twice daily on days 1 through 5 and 8 through 12 in a 28-day cycle plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 of a 28-day treatment cycle, or capecitabine at 1250 or 1000 mg/m2
twice daily on days 1 through 14 of a 21-day cycle plus bevacizumab at 7.5 mg/kg on day 1 in of a 21-day cycle. A total of 77 patients received the trifluridine/tipiracil regimen and 76 patients were treated with the capecitabine combination.
Patient characteristics were balanced between treatment arms, with the exception that more patients in the trifluridine/tipiracil arm (39% vs 25%) had primary tumours located in the right colon compared with the capecitabine arm (39% vs 25%), which is a known indicator of poor survival.
The primary endpoint of the trial was PFS and the secondary endpoints included overall survival, safety and quality of life assessed using the EORTC QLQ-C30 and QLQ-CR29 questionnaires.
Subgroups under analysis included RAS
mutation status, ECOG performance status, gender, and neutrophil versus lymphocyte count. PFS favored capecitabine and bevacizumab only in patients with liver metastasis at baseline (HR, 1.58).
“Overall survival data are not yet mature, but follows a trend that is consistent with PFS,” Van Cutsem noted.
The incidence of any treatment-emergent adverse events (AEs) and any serious event was similar with both treatments. However, the incidence of grade ≥3 AEs was higher with trifluridine/tipiracil at 77.9% versus 43.4% in the capecitabine arm. AEs led to study withdrawal in 40.3% versus 36.8% of patients in the respective arms.
With trifluridine/tipiracil plus bevacizumab, 4 (5.2%) patients died on study compared with 9 (11.8%) of patients receiving capecitabine plus bevacizumab.
“What is interesting is that treatment with trifluridine /tipiracil plus bevacizumab is feasible and effective in this population of patients with previously untreated metastatic colorectal cancer who were not eligible for treatment with standard chemotherapy and were not candidates for surgical resection,” Van Cutsem said.
Lesniewski-Kmak K, Moiseenko V, Saunders M, et al. Phase II study evaluating trifluridine/tipiracil + bevacizumab and capecitabine + bevacizumab in first-line unresectable metastatic colorectal cancer (mCRC) patients who are non-eligible for intensive therapy (TASCO1): results of the primary analysis. Ann Oncol. 2018;29 (suppl 5; abstr O-022).