ASCO GI 2026 Highlights: PARP Inhibitors Plus Immunotherapy
Key Points
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Early-phase trials are exploring combinations of PARP inhibitors and immunotherapy in gastrointestinal (GI) malignancies.
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In metastatic pancreatic cancer with DNA damage repair gene alterations, olaparib plus durvalumab has outcomes comparable to single-agent maintenance olaparib.
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KRAS inhibitors represent a promising targeted therapy option for pancreatic cancers.
PARP Inhibitors Plus Immunotherapy
At the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI 2026), Kriti Ahuja, MBBS, of Roswell Park Comprehensive Cancer Center, asked Dina Ioffe, MD, of Fox Chase Cancer Center, about the biological rationale and existing early data for combining PARP inhibitors and immunotherapy in GI malignancies.
PARP inhibitors block DNA repair, and in tumors with defects such as BRCA mutations or homologous recombination deficiency, PARP inhibition can lead to increased mutational burden, neoantigen generation, and PD-L1 expression in tumor cells. Together, these effects create a “hot” tumor immune microenvironment that is theoretically more sensitive to immunotherapy. PARP inhibitor-immune checkpoint inhibitor combinations have shown less efficacy r in GI tumors than in other disease sites, said Dr. Ioffe.
At ASCO GI 2026, authors presented preliminary data from a phase 2 trial on olaparib plus durvalumab after chemotherapy in metastatic pancreatic cancer with DNA damage repair gene alterations. The outcomes with the combination were similar to those reported with single-agent maintenance olaparib in the POLO trial, said Dr. Ioffe. She acknowledged that efficacy conclusions can’t be based on cross-trial comparisons, and suggested that more data are needed to see how much benefit is gained by adding immunotherapy to PARP inhibitors given the potential for increased toxicity.
The discussion turned to other meaningful research from this year’s conference. Dr. Ioffe highlighted emerging data supporting KRAS inhibitors in pancreatic cancers. “We’ve been using the same chemotherapy combinations for a very long time, so it’s exciting to have new potential targets in a very aggressive disease with a historically poor prognosis where there haven’t been a lot of targeted therapies,” said Dr. Ioffe.