Marcus Noel, MD
Susan Tsai, MD, MHS
Marcus Noel, MD, Associate Professor of Medicine at Lombardi Comprehensive Cancer Center and MedStar Georgetown University Hospital, Washington, DC, included SWOG S1505 in the presentation of the Gastrointestinal Cancer Highlights during the ASCO20 Virtual Scientific Program. Susan Tsai, MD, MHS, a surgical oncologist associated with LaBahn Pancreatic Cancer Program at the Medical College of Wisconsin, was the invited discussant of the study. Both agreed that neoadjuvant therapy may bypass some of the common obstacles in optimally treating pancreatic cancer.
“The standard of care in resectable pancreatic cancer is upfront surgery followed by adjuvant chemotherapy; however, patients who undergo surgery can suffer from complications and thus may not receive all their adjuvant therapy,” Dr. Noel pointed out.
Dr. Tsai estimated this group of patients (ie, those not able to receive adjuvant therapy) to account for about 50% of all patients planned for resection and adjuvant therapy, based on the real-world experience of several thousand patients in clinical trials. Another disincentive of upfront surgery, she added, is the high risk for positive margins. “In what other solid tumor do we accept an R1 rate of 40% to 60%?” she asked.
“Neoadjuvant therapy was conceived as a way to identify patients who are at highest risk for developing metastatic recurrence…to select patients who develop [or will develop] disease progression and to spare them the morbidity of an operation,” Dr. Tsai said.
According to Dr. Noel, the high potential for metastatic disease that already exists for newly diagnosed patients points to a role for neoadjuvant therapy, “the goal being to eliminate micrometastatic disease and hopefully improve overall survival,” Dr. Tsai said. “Sequencing of treatment may matter,” she added.
Comparable Efficacy in SWOG S1505
Thus, SWOG S1505 aimed to determine which of these current treatments may better accomplish these goals: modified FOLFIRINOX (leucovorin, fluorouracil, irinotecan, oxaliplatin) or gemcitabine/nab-paclitaxel. The regimens proved to be comparable in efficacy. “Overall survival in the study may have been lower than anticipated, but the study enrolled all comers,” Dr. Noel commented. “Traditional trials of adjuvant therapy enroll patients proven to be fit enough after surgery, whereas in S1505, patients were randomly assigned prior to any treatment, so we would expect lower overall survival.”
SWOG S1505 showed equivalence between the two regimens when given in the preoperative and postoperative settings, but gemcitabine/nab-paclitaxel was particularly “impressive” in terms of pathologic complete response (40%), noted Dr. Noel. “This was probably higher than most of us expected.”
Adjuvant vs Neoadjuvant Therapy
Although SWOG S1505 was not designed to answer the question of adjuvant vs neoadjuvant therapy, another study reported at the ASCO meeting—ESPAC-5F—did so in patients with borderline resectable disease. The investigators showed R0 resection rates were equivalent between upfront surgery and neoadjuvant therapy, but 1-year overall survival was improved with neoadjuvant therapy (77% vs 40%; hazard ratio = 0.27; P < .001).1
Given the results of SWOG S1505, ESPAC-5F, and the previous PREOPANC-1 trial,2 Dr. Tsai considers neoadjuvant therapy to be the preferred upfront treatment of operable pancreatic cancer. She further suggested that future trials will define the optimal preoperative regimen and will address other areas where clinical care could be improved, particularly in tumor staging and supportive care.
DISCLOSURE: Dr. Noel has served as a consultant or advisor to and served on the speakers bureaus for Celgene and Taiho Pharmaceutical. Dr. Tsai reported no conflicts of interest.
REFERENCES
1. Ghaneh P, Palmer DH, Cicconi S, et al: ESPAC-5F: Four-arm, prospective, multicenter, international randomized phase II trial of immediate surgery compared with neoadjuvant gemcitabine plus capecitabine or FOLFIRINOX or chemoradiotherapy in patients with borderline resectable pancreatic cancer. ASCO20 Virtual Scientific Program. Abstract 4505.
2. Van Tienhoven G, Versteijne E, Suker M, et al: Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1). 2018 ASCO Annual Meeting. Abstract LBA4002. Presented June 4, 2018.
