Abstract 320P
Background
Clinical trial eligibility criteria balance the competing interests of maximizing generalizability and maintaining patient safety. Overly restrictive criteria can limit patients’ access to effective drugs. Study of the patterns of ineligibility in patients with advanced BTC may shed light on opportunities to reconsider common eligibility criteria and accelerate drug development.
Methods
This study evaluated both the heterogeneity of eligibility criteria used in advanced biliary tract cancer clinical trials and also the impact of those criteria on patient eligibility in the real world. Selected clinical trials evaluated one or more systemic therapies in the second-line setting, and the patient cohort included patients who received at least two lines of systemic therapy for advanced BTC. We compared common trial eligibility criteria to patient data collected within 30 days of cycle 1 day 1 of second-line therapy to determine the frequency of potential ineligibility.
Results
Among 97 clinical trials screened, 37 met eligibility and evaluated targeted therapy (46%), chemotherapy (24%), immunotherapy (5%), or a combination of types of systemic therapies (24%). Of 879 patients screened, 290 (33%) met criteria for inclusion. Our findings highlighted variability in eligibility parameters. Trials excluded patients with a GFR cutoff of 30, 40, 50, or 60 mL/min, with the 60 mL/min cut-off excluding 20% of patients. Hemoglobin cut-offs varied from 8 to 10 g/dL, with a 10 g/dL cut-off excluding 30% of patients. Criteria that lacked time limitations, such as excluding patients with “any history” of prior malignancy, risked excluding more patients (12.6%) than those with limitations (2.5% of patients excluded with a 2 year cut-off). Trials frequently excluded marginalized groups such as patients with HIV (41% of trials) or asymptomatic brain metastases (32%).
Conclusions
To broaden eligibility criteria and mitigate variability, we propose a set of standardized eligibility criteria for use in advanced BTC trials. Implementing these criteria, with exceptions for pharmacology, toxicity profile, and/or mechanism of action of study drugs, may enable access to novel therapies to a broader range of individuals without sacrificing patient safety.
Legal entity responsible for the study
The authors.
Funding
LG receives funding from the American Cancer Society Clinical Scientist Development Grant 134013-CSDG-19-163-01-TBG, the NIH/NCI Gastrointestinal Cancer SPORE P50 CA127003, V Foundation for Cancer Research Translational Grant, and the Cholangiocarcinoma Foundation Andrea Marie Fuquay Research Fellowship.
Disclosure
L. Goyal: Financial Interests, Advisory Board: Alentis Therapeutics, Black Diamond, Blueprint Medicine, Basilea, Genentech, Exelixis, H3Biomedicine, Incyte Corporation, Kinnate, QED Therapeutics, The Servier Group, SIRTEX, Taiho Oncology, Transthera Bio, AstraZeneca. All other authors have declared no conflicts of interest.