Randomized Phase II Study of PARP Inhibitor Veliparib with Modified FOLFIRI versus FOLFIRI as Second Line Treatment of Metastatic Pancreatic Cancer: SWOG S1513.

PURPOSE: Poly (ADP-ribose) polymerase (PARP) inhibitors synergize with topoisomerase inhibitors, and veliparib plus modified (m) FOLFIRI (no 5-FU bolus) had preliminary activity in metastatic pancreatic cancers (mPC). This study evaluated the safety and efficacy of second-line treatment with veliparib and mFOLFIRI vs FOLFIRI (control) for mPC.

EXPERIMENTAL DESIGN: This randomized phase II clinical trial led by the SWOG Cancer Research Network enrolled patients between September 1, 2016 and December 13, 2017. The median follow-up was 9 months (IQR 1-27). BRCA1/2 and homologous recombination DNA damage repair (HR-DDR) genetic defects were tested in blood and tumor biopsies. Patients received veliparib 200 mg twice daily, days 1-7 with mFOLFIRI days 3-5, or FOLFIRI in 14 days-cycles.

RESULTS: After 123 of planned 143 patients were accrued, an interim futility analysis indicated the veliparib arm was unlikely to be superior to control, and the study was halted. Median survival (OS) was 5.4 vs 6.5 months (HR 1.23, p=0.28), and median progression free survival (PFS) was 2.1 vs 2.9 months (HR 1.39, p=0.09) with veliparib vs control. Grade 3/4 toxicities were more common with veliparib (69% vs 58%, p=0.23). For cancers with HR-DDR defects vs wild type, median PFS and OS were 7.3 vs 2.5 months (p=0.05), and 10.1 vs 5.9 months (p=0.17), respectively with FOLFIRI, and 2.0 vs 2.1 months (p=0.62) and 7.4 vs 5.1 months (p=0.10), respectively with veliparib plus mFOLFIRI.

CONCLUSIONS: Veliparib plus mFOLFIRI did not improve survival for mPC. FOLFIRI should be further studied in pancreatic cancers with HR-DDR defects.