Higher OS With Neoadjuvant Chemo-RT in Pancreatic Cancer


In PREOPANC, the 2-year survival rate was significantly higher for patients who received neoadjuvant chemoradiotherapy vs standard care.

Undergoing chemoradiotherapy prior to surgery improved outcomes in patients with borderline resectable pancreatic cancer as compared to having immediate surgery, a new study has found. Patients who received neoadjuvant chemoradiotherapy had a significantly improved median overall survival (OS) of 17.1 months, compared with an OS of 13.5 months for those who did not (hazard ratio [HR], 0.74; P = .047).

“These preliminary results of [the] PREOPANC [study] suggest a benefit of preoperative radiochemotherapy over immediate surgery,” said radiation oncologist Geertjan Van Tienhoven, MD, PhD, from the Department of Radiation Oncology, Academic Medical Center in Amsterdam. Van Tienhoven presented the results at a press conference at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.

Van Tienhoven stressed that these results are preliminary. “We still need 26 more events before the final analysis, and the final results have to be awaited before we can draw definitive conclusions,” he said. “But these results suggest a benefit for chemoradiation prior to surgery over surgery and adjuvant chemotherapy."

The standard of care for patients with borderline resectable pancreatic adenocarcinoma is surgery followed by adjuvant chemotherapy, but resection is only possible in about 15% to 20% of patients. Even after successful surgery, recurrence is common and many patients will eventually succumb to the disease.

Data from previous studies have suggested a benefit for neoadjuvant therapy in this population, and Van Tienhoven and colleagues conducted a phase III randomized controlled trial to evaluate this approach in patients with resectable tumors.

The PREOPANC-1 study enrolled 246 patients who were randomly assigned to receive preoperative chemoradiotherapy (2.4 Gy for 15 rounds plus gemcitabine at 1,000 mg/m2) or immediate surgery. Patients in both arms also received adjuvant chemotherapy with gemcitabine. The study’s primary endpoint was OS, and secondary endpoints included microscopically complete (R0) resection rate, disease-free survival, distant metastasis-free interval, locoregional recurrence-free interval, and safety. At the cutoff date for analysis, 142 of the 176 needed events for the primary outcome had occurred.

A total of 72 patients (60%) in the neoadjuvant arm underwent surgery vs 91 patients (72%) in the immediate-surgery group (P = .065). The 2-year survival rate was higher for patients who received neoadjuvant chemoradiotherapy vs standard care (42% vs 30%). All other outcomes also favored the neoadjuvant treatment arm.

The R0 resection rate (31% vs 63%; P ≤ .001), median disease-free survival (7.9 months vs 11.2 months; HR, 0.71; P = .023), median distant metastases–free interval (10.2 months vs 17.1 months; HR, 0.71; P = .013), and median locoregional recurrence-free interval (11.8 months vs not reached; HR, 0.55; P < .002).

In a subset analysis of patients who underwent R0/R1 resection, the difference in median survival was even greater with preoperative treatment (42.1 months vs 16.8 months; P < .001).

Disease progression occurred in 80% of those receiving standard care vs 50% in the neoadjuvant group (P = .002), while the mortality rate was high in both arms: 65% in the standard treatment arm compared with 55% in the neoadjuvant arm (P = .074).

ASCO Expert Andrew S. Epstein, MD, of Memorial Sloan Kettering Cancer Center in New York City, commented that this is an important randomized study which is hard to conduct in a disease like this one. “Looking at preoperative therapy is particularly important, and I eagerly await the final results,” he said. “I think it’s an important step in what we know about this illness, particularly [regarding] the role of radiation in this setting.”

Data on the use of radiation postoperatively have been mixed, “so I commend the authors for doing it upfront and contributing to what we know about what may help these patients with pancreas cancer who might ultimately get surgery,” Epstein said.

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