1. Goodwin, Peter M.

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CHICAGO-Patients with resectable and "borderline resectable" pancreatic cancers treated with chemoradiation before surgery (followed by adjuvant chemotherapy) had significantly improved outcomes compared to those randomized to have surgery first and adjuvant chemotherapy in the Dutch Pancreatic Cancer Group's PREOPANC-1 randomized, controlled, multicenter, phase III trial reported at the 2018 ASCO Annual Meeting (Abstract LBA4002).

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Although fewer tumors could be resected in patients treated with preoperative therapy compared with those on standard care (down from 72 percent to 62 percent), there was a markedly increased rate of complete resections, said study author Geertjan Van Tienhoven MD, PhD, a radiation oncologist at the Academic Medical Center in Amsterdam, Netherlands, who is a member of the Dutch Pancreatic Cancer Group.


"We found that preoperative chemoradiotherapy improved all of the endpoints. The microscopically complete resection rate was doubled. The local control was improved significantly. The metastasis-free interval and disease-free survival were improved significantly," he noted.


Overall Survival

Overall survival (OS)-the primary endpoint of PREOPANC-1-was also improved, Van Tienhoven said, but the data did not reach statistical significance (p=0.074). Median OS in patients who had preoperative chemoradiotherapy was 17.1 months, compared with 13.5 months for usual care. This translated to 42 percent of patients in the experimental arm surviving at least 2 years, compared with 30 percent of patients on standard treatment.


Van Tienhoven told Oncology Times they hoped to confirm a statistically significant improvement of OS in a few months time when there would have been sufficient events. (At the time of reporting, only 142 events had been observed out of the 176 needed.)


PREOPANC-1 randomized 246 patients with resectable or borderline resectable pancreatic cancer (in 17 hospitals in the Netherlands) to immediate surgery or preoperative chemoradiotherapy followed by surgical resection. Patients in both arms of the study also had postoperative adjuvant chemotherapy. Preoperative treatment consisted of 15 daily fractions of 2.4 Gy given concurrently with gemcitabine (1,000 mg/m2) chemotherapy on day 1 followed by two more doses of gemcitabine on day 8 and day 15. All patients received the same total dose of chemotherapy.


Other Outcomes

In patients treated with preoperative therapy, the complete resection rate went up from 31 percent to 65 percent compared to patients having surgery first. Median disease-free survival increased from 7.9 months to 11.2 months. In a subgroup analysis of patients who actually had resections, median OS went up from 16.8 months on standard treatment to 29.9 months among those treated preoperatively. In the subset of patients having preoperative treatment in whom the tumor was removed successfully, median OS was 42.1 months compared with 16.8 months among patients who had immediate surgery, Van Tienhoven explained.


The distant metastasis-free interval went up in the experimental arm to 17.1 months from a median of 10.2 months for patients on standard therapy. The change in local relapse-free interval was even more marked, increasing from a median of 11.8 months to "not reached" among patients on preoperative chemo-radiotherapy.


There were no significant differences in grade 3 or higher adverse events between the arms of the study.


When he was asked about the preliminary message for doctors coming out of these data in such a difficult disease setting, Van Tienhoven noted the results were hopeful and that they were consistent with a paradigm shift toward preoperative therapy for pancreas cancer.


"Up to now, [this] is the only randomized trial on this," he observed. But he thought the PREOPANC-1 data were likely to have an impact in the clinic. "We believe that this may be a practice-changing trial," he said in a press briefing at ASCO.


ASCO expert Andrew Epstein, MD, Hospice and Palliative Instructor in Medicine and Assistant Attending Physician at Memorial Sloan-Kettering Cancer Center, and Assistant Professor of Medicine at Weill Cornell Medical College, New York City, noted: "This study is an example of how treatments can be refined in an attempt to work better for patients. It's also a step in the right direction for people with pancreatic cancer, a disease that has proved extremely difficult to cure."


Van Tienhoven's recommendation to doctors was to introduce patients to the idea that doing immediate surgery was not necessarily in their best interests. "If we can explain to them that they are better off when we do chemotherapy or chemo-radiotherapy first, they will accept that."


He said that since preoperative chemo-radiotherapy had already been adopted in esophageal cancer around the world, this was likely for pancreatic cancer. "At this moment in time, preoperative chemo-radiotherapy is a good alternative to upfront surgery followed by adjuvant treatment."


Peter M. Goodwin is a contributing writer.