Abstract 285P
Background
Biliary tract cancer (BTC) represents a rare group of tumors associated with a poor prognosis. Cisplatin and gemcitabine, recently combined with PD-(L)1 inhibitor, represent the first-line standard of care for advanced BTC, and oxaliplatin is often considered an alternative to cisplatin. In this investigator-initiated multicenter, single-arm, phase I/II trial, we investigated safety and activity of gemcitabine, oxaliplatin and nab-paclitaxel as first-line treatment for patients (pts) with advanced BTC.
Methods
Patients were accrued into cohorts of 3 pts and dose escalation was performed following the 3+3 rule. The phase I primary objective was to assess maximum tolerated dose (MTD) and recommended phase II dose (RP2D). The primary endpoint of the study was the proportion of pts free from progression at 6 months. Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response.
Results
From July 2017 to December 2020, 78 pts were enrolled, 10 pts were screen failure, 68 pts were eligible, 67 pts started treatment. Median age was 65 (range 39-77) years, most pts had iCCA (58.20%), and metastatic disease (74.62%). No dose-limiting toxicity was observed in the phase I (10 pts), dose level 2 (gemcitabine 1000 mg/m2 + oxaliplatin 80 mg/m2 + nab-paclitaxel 150 mg/m2) was defined as RP2D. We observed 339 AEs, 59.88% were considered drug-related (DR), 3.24% were DR and serious. Most common DRAEs were G3 neutropenia and G1-2 peripheral neuropathy. Four patients had G5 AEs including DR sepsis, non-DR biliary tract infection, hepatic failure, hyponatremia (1 pt each). Median follow-up was 26 months (range 0.3-56). At the data cutoff, the proportion of pts free from progression at 6 months was 49.1% (95% CI 40.8-57.5). Median PFS was 6.3 months (95% CI 3.6-10.1), median OS 12.4 month (95% CI 8-23), ORR 20.89%, and disease-control rate 67.15%.
Conclusions
This study did not meet its primary endpoint however, the tested regimen showed a good safety profile. Ongoing research will clarify the role of chemotherapy combinations in different settings.
Clinical trial identification
NCT03943043.
Legal entity responsible for the study
The authors.
Funding
The trial received funding from Celgene Italy which supplied nab-paclitaxel and financial support with no other role of any kind.
Disclosure
T. Pressiani: Financial Interests, Other, Consulting fees: Bayer, Ipsen, AstraZeneca; Financial Interests, Other, Institutional research funding: Roche, Bayer, AstraZeneca; Financial Interests, Other, Travel Expenses: Roche. R. Balsano: Financial Interests, Other, Lectures fees: AstraZeneca; Financial Interests, Other, Travel Expenses: Roche. M. Milella: Financial Interests, Other, Personal Honoraria: AstraZeneca, MSD Oncology, Ipsen, Hippocrates Research, Viatris, Servier; Financial Interests, Other, Consulting or Advisory role: AstraZeneca, MSD Oncology, Janssen Oncology; Financial Interests, Other, Steering Committee, Data Monitoring Committee: Novartis, OncoSil; Financial Interests, Other, Institutional Research Funding: Roche. F. Bergamo: Financial Interests, Other, Personal honoraria as invited speaker: Eli Lilly, MSD, Eisai, Bristol Myers Squibb, AstraZeneca, Pierre Fabre; Financial Interests, Advisory Board: Servier, AAA Novartis. D. Ferrari: Financial Interests, Other, Lecture fees: MSD. H.J. Soto Parra: Financial Interests, Advisory Board: Merck Sharpe & Dohme, Bristol Myers Squibb, Pfizer, Roche, Takeda, AstraZeneca, Eli Lilly, Sanofi. C. Soldà: Financial Interests, Other, Consulting or advisory role: MSD, Eisai; Financial Interests, Speaker’s Bureau: Roche, MSD. A. Zaniboni: Financial Interests, Speaker’s Bureau: Merck Serono, Amgen, Servier, Sanofi, MSD. L. Rimassa: Financial Interests, Other, Consulting fees: AbbVie, AstraZeneca, Basilea, Bayer, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incute, Ipsen, qvia, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; Financial Interests, Other, Lecture fees: AstraZeneca, Bayer, BMS, Incyte, Ipsen, Roche, Servier; Financial Interests, Other, Travel expenses: AstraZeneca; Financial Interests, Other, Institutional research funding: Agios, AstraZeneca, BeiGene, Eisai, Exelixis, FibroGen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Zymeworks. A. Santoro: Financial Interests, Advisory Board: BMS (Bristol Myers Squibb), Servier, Gilead, Pfizer, Eisai, Bayer, MSD (Merck Sharp & Dohme); Financial Interests, Other, Consulting fees: Sanofi, Incyte; Financial Interests, Speaker’s Bureau: Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD, BeiGene. All other authors have declared no conflicts of interest.