Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513
Year: 2021
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Purpose: PARP inhibitors synergize with topoisomerase inhibitors, and veliparib plus modified (m) FOLFIRI (no 5-FU bolus) had preliminary activity in metastatic pancreatic cancers. This study evaluated the safety and efficacy of second-line treatment with veliparib and mFOLFIRI versus FOLFIRI (control) for metastatic pancreatic cancer. Patients and Methods: 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-day cycles. Results: After 123 of planned 143 patients were accrued, an interim futility analysis indicated that the veliparib arm was unlikely to be superior to control, and the study was halted. Median overall survival (OS) was 5.4 versus 6.5 months (HR, 1.23; P = 0.28), and median progression-free survival (PFS) was 2.1 versus 2.9 months (HR, 1.39; P = 0.09) with veliparib versus control. Grade 3/4 toxicities were more common with veliparib (69% vs. 58%, P = 0.23). For cancers with HR-DDR defects versus wild-type, median PFS and OS were 7.3 versus 2.5 months (P = 0.05) and 10.1 versus 5.9 months (P = 0.17), respectively, with FOLFIRI, and 2.0 versus 2.1 months (P = 0.62) and 7.4 versus 5.1 months (P = 0.10), respectively, with veliparib plus mFOLFIRI. Conclusions: Veliparib plus mFOLFIRI did not improve survival for metastatic pancreatic cancer. FOLFIRI should be further studied in pancreatic cancers with HR-DDR defects.
Source: Clinical Cancer Research
Authors: E. Gabriela Chiorean, Katherine A. Guthrie, Philip A. Philip, Elizabeth M. Swisher, Florencia Jalikis, Michael J. Pishvaian, Jordan Berlin, Marcus S. Noel, Jennifer M. Suga, Ignacio Garrido-Laguna, Dana Backlund Cardin, Marc R. Radke, Mai Duong, Shay Bellasea, Andrew M. Lowy, Howard S. Hochster
Institutions: University of Washington, Fred Hutch Cancer Center, Wayne State University, The Barbara Ann Karmanos Cancer Institute, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Johns Hopkins University, Georgetown University, Georgetown Lombardi Comprehensive Cancer Center, Kaiser Permanente, Kaiser Permanente Vallejo Medical Center, University of Utah, Huntsman Cancer Institute, University of California San Diego, Moores Cancer Center, Rutgers Cancer Institute
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1044130170, G1266999854, G1347238333, G1548551769, G157993030, G1653603600, ECOG-ACRIN Network Group Operations Center, G1938688226, G1974211183, G2002724969, G2053330539, G2061465891, G2117393317, G2406815399, G2509465741, G2692124468, G2934225706, G332150848, G333286927, G3337849518, G3357380961, City of Hope Southwest Oncology Group Clinical Trials, G3650305600, SWOG Network Group Operations Center of the NCTN, G399916856, G4017138494, G4289044101, G4468683055, Nemours NCI Community Oncology Research Program (NCORP), G4768247927, G4768276527, G5245746260, G5448779787, G5543259819, G5645591806, G5671623325, G594289469, G6078212843, Cancer Research Consortium of West Michigan (CRCWM), G6520121107, G6880957883, G6970698343, Yale Cancer Center NCTN, G7081193278, G7367166394, G7451701487, G7852806821, G814179290, CIRI Oncology Research Alliance, G860041726, Alliance for Clinical Trials in Oncology Operations Center, Montana Cancer Consortium: An Inclusive and Collaborative Approach to Clinical Trial Accrual and Cancer Care Delivery Research across Montana, Idaho and Wyoming, G8898045420, G9000075442, G9000097697, G9000101549, G9000113362, G9000119871, G9000135971, G9000182428, G9000207388, G9000207544, G9000214104, G9000218998, G9000220179, G9000233257, G9000237600, G9000240063, G9000240473, G9000241563, G9000244569, G9000284858, G9000291439, G9000327168, G9000339467, Yale Clinical and Translational Science Award, G93539815
OpenAlex ID: W3204487449