Dr Wainberg on Treatment Updates in Gastric Cancer and Biliary Tract Cancer

"We saw for the first time some evidence that there is a reasonable control rate with olaparib in this group of patients with homologous recombination repair deficiencies.We've known about this for a while, but this was the first study to look at that show some modest activity. We're waiting for the next few studies which are combining with different agents"

Zev A. Wainberg, MD, MSc, a professor of medicine in the Department of Medicine at UCLA and co-director of the UCLA GI Oncology Program, highlighted several key studies in gastric and biliary tract cancer that were presented during the 2025 ESMO GI Congress.

Wainberg began by discussing emerging evidence for PARP inhibitors in patients with homologous recombination repair (HRR) deficiencies. He noted this was the first study to show modest activity for this class of agents, reporting high disease control rate (DCR) with olaparib (Lynparza). There is an ongoing need for further studies combining PARP inhibitors with different agents and the critical importance of identifying these patients in advance, he emphasized.

Real-world evidence from the phase 3b ProvIDHe study (NCT05876754) evaluating ivosidenib (Tibsovo) in patients with IDH1-mutated cholangiocarcinoma showed a median progression-free survival (PFS) of 4.7 months (95% CI, 3.5-5.7) and a median overall survival (OS) of 15.5 months (95% CI, 12.7-not evaluable [NE]), Wainberg reported. This study, which enrolled 285 patients, reaffirmed ivosidenib’s role as a standard of care in the second-line setting for this patient population. Initial data also revealed an objective response rate of 5.7% (all partial responses) and a DCR of 51.5%, with a median duration of response of 10.1 months (95% CI, 3.0-NE). This real-world evidence from ProvIDHe was noted to confirm and support the original dataset from the phase 3 ClarIDHy study (NCT02989857), which led to ivosidenib's FDA approval in August 2021 for previously treated, locally advanced or metastatic IDH1-mutated cholangiocarcinoma.

In the realm of gastric cancer, a quality of life analysis from the phase 3 RATIONALE-305 study (NCT03777657) reaffirmed that patients who experienced clinical benefit with tislelizumab (Tevimbra) plus chemotherapy as first-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma also demonstrated symptomatic improvement, Wainberg detailed. This regimen yielded superior OS outcomes with a manageable safety profile. Finally, a retrospective review on hereditary diffuse gastric cancer challenged the notion of mandatory surgery for every patient, suggesting that advanced endoscopic techniques could be considered as an alternative to surgical intervention in certain cases, he concluded.