Randomized, multicenter, phase II trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germline BRCA/PALB2 mutation Journal Article
| Authors: | O'Reilly, E. M.; Lee, J. W.; Zalupski, M.; Capanu, M.; Park, J.; Golan, T.; Tahover, E.; Lowery, M. A.; Chou, J. F.; Sahai, V.; Brenner, R.; Kindler, H. L.; Yu, K. H.; Zervoudakis, A.; Vemuri, S.; Stadler, Z. K.; Do, R. K. G.; Dhani, N.; Chen, A. P.; Kelsen, D. P. |
| Article Title: | Randomized, multicenter, phase II trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germline BRCA/PALB2 mutation |
| Abstract: | PURPOSEFive percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (gBRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in gBRCA/PALB2+ PDAC.PATIENTS AND METHODSEligible patients had untreated gBRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m(2) and gemcitabine 600 mg/m(2) intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses.RESULTSFifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B (P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B (P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia.CONCLUSIONCisplatin and gemcitabine is an effective regimen in advanced gBRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in gBRCA/PALB2+ PDAC. |
| Keywords: | survival; resistance; landscape; cancer |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 38 |
| Issue: | 13 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2020-05-01 |
| Start Page: | 1378 |
| End Page: | 1388 |
| Language: | English |
| ACCESSION: | WOS:000537765800003 |
| DOI: | 10.1200/jco.19.02931 |
| PROVIDER: | wos |
| PMCID: | PMC7193749 |
| PUBMED: | 31976786 |
| Notes: | Article -- Source: Wos |
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