99P - Bevacizumab plus erlotinib maintenance versus observation in advanced biliary tract cancers: Results from the phase II component of a prospective integrated phase II-phase III parallel design superiority clinical trial (BEER-BTC study)

Background

Patients with chemotherapy-responsive advanced biliary tract cancer (BTC) are usually observed post 6 months of gemcitabine-based therapy, though most progress within a short time-span and there is limited prospective evidence for maintenance strategies.

Methods

The study is an integrated phase II – III randomised clinical trial (Clinical Trial Registry of India number: CTRI/2017/10/010112) conducted at 2 centres in India. Eligible patients with advanced BTC who had responsive or stable disease status post 6 months of gemcitabine – based chemotherapy were randomly assigned (1:1) to either observation arm (O) or intervention arm (BEER), which was a combination of Bevacizumab 5 mg/m2 IV every 21 days plus erlotinib 100 mg once daily, . Both arms were continued till disease progression, significant toxicity or patients choice. The primary endpoint of the phase II component was progression free survival, measured from randomization into the trial.

Results

Between May 2021 and November 2022, 98 patients (O: 48; BEER: 50) comprising 78 patients with gallbladder cancer (GBC) and 20 patients with cholangiocarcinoma (CC) were randomised with all 98 patients included in the final analysis. With a median follow up of 11.2 months, patients in the BEER cohort showed an improved PFS compared to the observation cohort [5.2 months (95% CI: 3.4-6.9) vs. 3 months (95% CI: 2.5 - 3.5); p=0.004]. The CC cohort tended to derive greater benefit from BEER (6.7 months vs. 2.2 months) than the GBC cohort (4.3 months vs. 3 months). There were no grade 3 or grade 4 adverse events noted, though temporary cessation of erlotinib was required due to grade 2 skin rash in 7 patients (14%), and grade 2 oral stomatitis in 1 patient (2%).

Conclusions

The combination of bevacizumab and erlotinib improves progression free survival in patients with chemotherapy responsive advanced BTC in this phase 2 clinical trial. The ongoing phase III component of the study will evaluate whether the significant benefit in PFS translates to improvement in overall survival.

Clinical trial identification

CTRI/2017/10/010112.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Cadilla Pharma Pvt Ltd (supported bevacizumab) Dr. Reddy's Lab pvt Ltd (supported bevacizumab) LUPIN Pharma pvt Ltd Intas pvt Ltd.

Disclosure

A. Ramaswamy: Financial Interests, Institutional, Research Grant: Cipla Health Limited, Dr Reddy Laboratories, Zydus Lifesciences. V.S. Ostwal: Financial Interests, Institutional, Funding, IIS: Cadilla Pharmaceuticals pvt Lts, Reddy's pvt Ltd, Lupin, BDR; Financial Interests, Personal, Invited Speaker, GI ESMO 22: AstraZeneca; Financial Interests, Institutional, Advisory Board: Mankind, Natco. All other authors have declared no conflicts of interest.