TY - JOUR
T1 - Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer
T2 - SWOG S1513
AU - Chiorean, E. Gabriela
AU - Guthrie, Katherine A.
AU - Philip, Philip A.
AU - Swisher, Elizabeth M.
AU - Jalikis, Florencia
AU - Pishvaian, Michael J.
AU - Berlin, Jordan
AU - Noel, Marcus S.
AU - Suga, Jennifer M.
AU - Garrido-Laguna, Ignacio
AU - Cardin, Dana Backlund
AU - Radke, Marc R.
AU - Duong, Mai
AU - Bellasea, Shay
AU - Lowy, Andrew M.
AU - Hochster, Howard S.
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research Inc.. All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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 (IQR1-27).BRCA1/2 andhomologous 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 progressionfree 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. _2021 American Association for Cancer Research.
AB - 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 (IQR1-27).BRCA1/2 andhomologous 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 progressionfree 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. _2021 American Association for Cancer Research.
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U2 - 10.1158/1078-0432.CCR-21-1789
DO - 10.1158/1078-0432.CCR-21-1789
M3 - Article
C2 - 34580114
AN - SCOPUS:85120457947
SN - 1078-0432
VL - 27
SP - 6314
EP - 6322
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -