Study details
The trial was conducted among 52 patients with untreated locally advanced or metastatic pancreatic ductal adenocarcinoma. Fully 94% had a BRCA mutation, while the rest had a PALB2 mutation, according to data reported at the symposium, sponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The response rate – the trial’s primary endpoint – was 65.2% with cisplatin-gemcitabine alone and 74.1% with cisplatin-gemcitabine plus veliparib (P = .55), with both arms far exceeding not only the 10% prespecified as “acceptable,” but also the 30% prespecified as “promising.” The respective disease control rates were 78.3% and 100% (P = .02).
Median progression-free survival was 9.7 months with chemotherapy alone and 10.1 months with chemotherapy plus the PARP inhibitor (P = .73). “If you reference an unselected population, that would be about 5 to 7 months,” Dr. O’Reilly noted. Median overall survival was 16.4 months and 15.5 months, respectively (P = .6). For the entire trial cohort, the 2-year overall survival rate was 30.6% and the 3-year overall survival rate was 17.8%.
“The combination came at the expense of hematologic toxicity,” Dr. O’Reilly said, with patients given veliparib having higher rates of grade 3 or 4 neutropenia (48% vs. 30%), thrombocytopenia (55% vs. 9%), and anemia (52% vs. 35%).
In an exploratory analysis among all patients receiving 4 or more months of chemotherapy and then continuing on or starting a PARP inhibitor as their next therapy, without disease progression, median overall survival was 23.4 months, very similar to what was seen in the POLO trial, she noted.
Dr. O’Reilly disclosed that she has ties with Vesselon, Polaris, and CytomX, and that her institution receives grant/research support from Celgene, Sanofi, Genentech-Roche, AstraZeneca, BMS, Silenseed, MabVax, Halozyme, and Acta Biologica. The trial was funded by the Lustgarten Foundation, the David M. Rubenstein Center for Pancreatic Cancer Research, the Reiss Family Foundation, the National Cancer Institute’s Cancer Therapy Evaluation Program, and NCI grants. Dr. Schilsky disclosed that he has no conflicts of interest.
SOURCE: O’Reilly EM et al. 2020 GI Cancers Symposium. Abstract 639.