Perioperative Gemcitabine + Erlotinib Plus Pancreaticoduodenectomy for Resectable Pancreatic Adenocarcinoma: ACOSOG Z5041 (Alliance) Phase II Trial
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There is considerable interest in a neoadjuvant approach for resectable pancreatic ductal adenocarcinoma (PDAC). This study evaluated perioperative gemcitabine + erlotinib (G+E) for resectable PDAC.
A multicenter, cooperative group, single-arm, phase II trial was conducted between April 2009 and November 2013 (ACOSOG Z5041). Patients with biopsy-confirmed PDAC in the pancreatic head without evidence of involvement of major mesenteric vessels (resectable) were eligible. Patients (n = 123) received an 8-week cycle of G+E before and after surgery. The primary endpoint was 2-year overall survival (OS), and secondary endpoints included toxicity, response, resection rate, and time to progression. Resectability was assessed retrospectively by central review. The study closed early due to slow accrual, and no formal hypothesis testing was performed.
Overall, 114 patients were eligible, consented, and initiated protocol treatment. By central radiologic review, 97 (85%) of the 114 patients met the protocol-defined resectability criteria. Grade 3+ toxicity was reported in 60% and 79% of patients during the neoadjuvant phase and overall, respectively. Twenty-two of 114 (19%) patients did not proceed to surgery; 83 patients (73%) were successfully resected. R0 and R1 margins were obtained in 67 (81%) and 16 (19%) resected patients, respectively, and 54 patients completed postoperative G+E (65%). The 2-year OS rate for the entire cohort (n = 114) was 40% (95% confidence interval [CI] 31–50), with a median OS of 21.3 months (95% CI 17.2–25.9). The 2-year OS rate for resected patients (n = 83) was 52% (95% CI 41–63), with a median OS of 25.4 months (95% CI 21.8–29.6).
For resectable PDAC, perioperative G+E is feasible. Further evaluation of neoadjuvant strategies in resectable PDAC is warranted with more active systemic regimens.
The authors would like to thank T.J. FitzGerald, MD, and staff at IROC Rhode Island [formerly the Quality Assurance Review Center (QARC)], especially Sandra Kessel and Deirdre Logan, for their support in acquisition of the diagnostic imaging and facilitation of the radiologic review. The following institutions enrolled patients to this study: University Health Network–Princess Margaret Cancer Centre, Laura and Isaac Perlmutter Cancer Center at NYU Langone, Vanderbilt University/Ingram Cancer Center, University of Chicago Comprehensive Cancer Center, UC Irvine Health/Chao Family Comprehensive Cancer Center, Medical College of Wisconsin, Memorial Sloan Kettering Medical Center, MD Anderson Cancer Center, West Virginia University Healthcare, University of Tennessee–Knoxville, Providence Portland Medical Center, Carolinas Medical Center/Levine Cancer Institute, UC San Diego Moores Cancer Center, Lakeland Regional Health Hollis Cancer Center, Ochsner Medical Center Jefferson, Saint Peter’s Health Partners, Piedmont Hospital, Henry Ford Hospital, University of Mississippi Medical Center, Kaiser Permanente Los Angeles Medical Center, Nebraska Methodist Hospital, Natalie Warren Bryant Cancer Center at Saint Francis, Loma Linda University Medical Center, Providence Sacred Heart Medical Center and Children’s Hospital, UNC Lineberger Comprehensive Cancer Center, Saint Luke’s University Hospital–Bethlehem Campus, University of Wisconsin Hospital and Clinics, Good Samaritan Hospital–Dayton, Miami Valley Hospital, Spartanburg Medical Center, and St. Vincent’s Medical Center.
Research reported in this publication was supported by the National Institutes of Health under award numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), U10CA180791, U10CA180836, U10CA180858, and U10CA180867, U24CA180803 (IROC), and U10CA29511 (QARC). This work was also supported in part by funds from OSI Pharmaceuticals, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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