4390 - Phase II trial of trifluridine/tipiracil (TAS-102) in patients with advanced refractory biliary tract cancer (BTC)

Background

Advanced BTC is an aggressive neoplasm with median overall survival (OS) of less than a year with current therapy. There is no approved second line therapy. TAS-102, a combination of the thymidine analog trifluridine, and tipiracil an inhibitor of trifluridine degradation, has shown activity in both fluoropyrimidine sensitive and resistant tumours. We conducted a single arm phase 2 trial to evaluate safety and efficacy of TAS-102 in pts with advanced, refractory BTC.

Methods

Pts of advanced BTC with ECOG PS 0-1 and adequate major organ function, who had progressed on at least one gemcitabine based chemotherapy, were enrolled and treated with TAS-102 at a dose of 35 mg/m2 BID on days 1-5 and 8-12 of a 28-day cycle until disease progression or unacceptable toxicity. The primary endpoint was 16-week progression-free survival (PFS) rate, defined as number of pts who are progression-free and alive at 16 weeks since registration (success) divided by the number of evaluable pts. Using a single stage binomial design, this study required 25 evaluable pts to compare a PFS rate at 16 weeks of 10% (null) versus 30% (alternative) with one-sided alpha of 0.05 and 80% power. Among the first 25 evaluable pts, 6 or more successes were needed for the regimen to be considered for further investigation. Secondary objectives included assessment of safety and tolerability, OS, response rate, and PFS.

Results

From 10/2017 to 8/2018, 28 pts were enrolled, of which 53.6 % pts were male and median age was 61.5 years (range: 46-77). 27 pts were evaluable for endpoint (1 patient did not start any treatment). PFS rate at 16 weeks was 9/27 [33.3%; 95% confidence interval (95% CI): 16.5-54.0 %]. Median (95% CI) PFS and OS were 3.9 (2.0 – 6.7) and 6.8 (5.8 – 12.3) months, respectively. The median number of treatment cycles was 3 (range: 1-8). Best response seen in this cohort was stable disease (13/27 pts). The most common grade 3 or worse adverse events were neutrophil count decreased (44.4%), anemia (22.2%), alkaline phosphate increased (22.2%), blood bilirubin increased (18.5%), and white blood cell decreased (18.5%) without any unexpected safety signals.

Conclusions

Treatment of advanced refractory BTC pts with TAS-102 demonstrated antitumor activity with acceptable toxicity.

Clinical trial identification

NCT03278106.

Editorial acknowledgement

Legal entity responsible for the study

Amit Mahipal.

Funding

Eisai.

Disclosure

All authors have declared no conflicts of interest.