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Perioperative chemotherapy feasible for resectable pancreatic adenocarcinoma
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CHICAGO — Perioperative chemotherapy appeared feasible for patients with resectable pancreatic adenocarcinoma, according to randomized phase 2 study results presented at ASCO Annual Meeting.
Safety results and resection rates also appeared encouraging, Davendra P.S. Sohal, MD, MPH, gastrointestinal medical oncologist and director of the clinical genomics program at Cleveland Clinic Taussig Cancer Institute, and colleagues concluded.
“This is the first-ever national study in the U.S. of perioperative chemotherapy for resectable pancreatic cancer,” Sohal told HemOnc Today. “It tests a new approach — to give chemotherapy upfront instead of the usual standard of surgery upfront.
“The main idea is to control systemic disease early with aggressive chemotherapy regimens to improve outcomes,” added Sohal, a HemOnc Today Next Gen Innovator. “Patients who are unable to tolerate chemotherapy or experience disease progression on preoperative chemotherapy are highly unlikely to be cured and, therefore, it is probably best to spare them a major operation.”
Clinical outcomes remain suboptimal for patients with resectable pancreatic ductal adenocarcinoma who receive curative therapy.
Sohal and colleagues conducted the prospective SWOG S1505 trial to evaluate aggressive perioperative chemotherapy — 12 weeks before surgery and 12 weeks after — for early control of systemic disease. This was the first such trial conducted in a National Clinical Trials Network setting.
Researchers enrolled 147 adults with confirmed tissue diagnosis of resectable pancreatic adenocarcinoma between 2015 and 2018. Investigators hoped to identify 100 eligible patients after accounting for cases deemed ineligible at central radiology review.
All patients had ECOG performance status of 0 or 1; no involvement of the celiac, common hepatic or superior mesenteric arteries; and no metastases.
Investigators assigned 74 patients to modified FOLFIRINOX, which consisted of 5-FU, irinotecan and oxaliplatin without bolus 5-FU and leucovorin. The other 73 patients received gemcitabine and nab-paclitaxel (Abraxane, Celgene).
Two-year OS — with a “pick-the-winner” study design to compare the two regimens — served as the primary outcome measure.
Forty-two patients (29%) were determined to be ineligible at central radiology review. Reasons for ineligibility included distant disease (n = 28), arterial involvement (n = 22), and venous involvement of 180 degrees or greater (n = 15). One other patient was ineligible due to distal cholangiocarcinoma, and one withdrew consent after randomization.
“Accrual was brisk, establishing feasibility,” Sohal and colleagues wrote. “Ineligible cases after central radiology review highlight quality control and physician education imperatives for neoadjuvant pancreatic adenocarcinoma trials.”
The final analysis included 103 eligible patients (median age, 64 years; 58% men; 89% white). Two-thirds (64%) of these patients had ECOG performance status of 0.
The majority of eligible patients started preoperative chemotherapy (96%) and completed the 3-month regimen (83%). Of those who started perioperative therapy, 76 (77%) went to surgery and 72 (73%) underwent resection.
“[The resection rate] is encouraging,” Sohal told HemOnc Today. “However, this is just the first step. We would like to improve [it] further.”
The primary reasons for not proceeding to surgery included chemotherapy toxicity and disease progression, Sohal said.
One patient died due to sepsis. Another 61 patients experienced grade 3 or grade 4 toxicities.
Researchers hypothesize that perioperative chemotherapy will prolong OS. Follow-up is continuing and OS data likely will be available in early 2020, Sohal said.
“[If the results are positive], the next steps would probably be selecting the more promising chemotherapy regimen based on this study and testing it in future trials of neoadjuvant chemotherapy, ideally with the addition of novel agents that could improve outcomes even further,” Sohal said. – by Mark Leiser
References:
Sohal D, et al. Abstract 4137. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Sohal reports honoraria and travel, accommodations or expenses from Foundation Medicine; a consultant/advisory role with Perthera; and research funding to his institution from Agios, Bayer, Bristol-Myers Squibb, Celgene, Genentech, Incyte, Novartis and OncoMed. Please see the abstract for all other authors’ relevant financial disclosures.