Abstract 4390
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.
Resources from the same session
2107 - Role of Individualized Intervention(s) on Quality of Life (QOL) and Adherence to Adjuvant Endocrine Therapy in Premenopausal Women with Early-Stage Breast Cancer (BC): MyChoice Study
Presenter: Shahid Ahmed
Session: Poster Display session 2
Resources:
Abstract
5812 - Correlation between the density of tumor-infiltrating lymphocytes, immune cell subsets in tumor stroma and response to systemic therapy in breast cancer
Presenter: Cvetka Grasic Kuhar
Session: Poster Display session 2
Resources:
Abstract
4734 - BRCA1/2 Testing in HER2- Advanced Breast Cancer (ABC): Results from the European Component of a Multi-Country Real World Study
Presenter: Michael Patrick Lux
Session: Poster Display session 2
Resources:
Abstract
1686 - In vitro and in vivo rescue of resistance to BET inhibitors by targeting PLK1 in triple negative breast cancer.
Presenter: Cristina Nieto-jiménez
Session: Poster Display session 2
Resources:
Abstract
5020 - Neoadjuvant endocrine therapy in combination with melatonin and metformin in locally advanced breast cancer
Presenter: Tatiana Semiglazova
Session: Poster Display session 2
Resources:
Abstract
5082 - Melatonin and metformin in neoadjuvant chemotherapy in locally advanced breast cancer
Presenter: Tatiana Semiglazova
Session: Poster Display session 2
Resources:
Abstract
2642 - Patient-tailored tamoxifen dosing based on an increased quantitative understanding of its complex pharmacokinetics: A novel integrative modelling approach
Presenter: Anna Mueller-Schoell
Session: Poster Display session 2
Resources:
Abstract
2461 - Lack of benefit of neoadjuvant pertuzumab in high risk HER2 positive breast cancer. A retrospective case-control study of 355 cases with biomarker analysis.
Presenter: Manuela Tiako Meyo
Session: Poster Display session 2
Resources:
Abstract
4776 - Targeting CDCA3 to improve chemotherapy response in triple-negative breast cancer patients
Presenter: Kenneth O'Byrne
Session: Poster Display session 2
Resources:
Abstract
1674 - Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer
Presenter: María Del Mar Noblejas López
Session: Poster Display session 2
Resources:
Abstract