CHICAGO -- Neoadjuvant chemoradiotherapy (CRT) may improve survival in patients with pancreatic cancer who are surgical candidates, according to findings from the randomized PREOPANC-1 trial.
In those with borderline or resectable disease, overall survival (OS) was 17.1 months with preoperative CRT versus 13.7 months with immediate surgery, but this failed to meet statistical significance (HR 0.74, P=0.074), reported Geertjan van Tienhoven, MD, PhD, of the Academic Medical Center in Amsterdam, the Netherlands, and collegues.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
More patients were alive in the CRT arm at 2 years (42% vs 30%), van Tienhoven reported during a press briefing here at the American Society of Clinical Oncology (ASCO) annual meeting.
He stressed that the results of this preoperative CRT approach are still preliminary, but that they "suggest benefit."
Though the primary endpoint of OS failed to reach statistical significance, a number of secondary endpoints favored the preoperative treatment arm. R0 resection rates were better (63% versus 31% with immediate surgery, P<0.001), as were rates of disease progression (50% versus 80%, P=0.002).
Rates of distant metastasis-free survival (HR 0.71, P=0.002) and locoregional-recurrence free interval (HR 0.55, P=0.002) also were better in the CRT arm.
ASCO expert Andrew Epstein, MD, of Memorial Sloan Kettering Cancer Center in New York City, told ľֱ that the results of the trial are not currently actionable. "I think that we need more data from this study, and I think we need more research looking at chemotherapy alone, preoperatively, for borderline patients," he said.
The study is complicated by the inclusion of resectable patients. "The heterogeneity makes it impossible to draw firm conclusions," said Epstein. "I think the notion of preoperative therapy most pertains to the borderline patients."
A randomized trial testing chemotherapy versus chemoradiotherapy in borderline patients only could help clarify the benefit of added radiation, which is still an "unanswered question," he stated.
Epstein suggested that an ideal preoperative trial might include a modified FOLFIRINOX regimen in borderline pancreatic patients who are fit enough for this more aggressive treatment.
"That being said, because pancreas cancer is a systemic illness and it's often recurrent, it might also be interesting to see a separate study looking at resectable patients," he noted.
But right now in patients with clearly resectable disease, Epstein said the results of another trial presented at ASCO -- surgery followed by adjuvant modified FOLFIRINOX -- would be best and is a new standard of care in resectable patients (more on this later from ľֱ).
The PREOPANC-1 trial enrolled 246 patients from 2013 to 2017. Patients in both arms were also treated with chemotherapy following surgery.
Preoperative CRT was comprised of 1,000 mg/m2 gemcitabine (Gemzar) on days 1, 8 and 15, combined with 15 fractions (2.4 Gy) of radiation therapy, a cycle of gemcitabine was also given before and after.
The intention-to-treat analysis included 127 patients randomized to immediate surgery and 119 randomized to CRT. "This is key," van Tienhoven said. "The analysis of such a trial should be done by intention to treat," so that doctors and patients cannot influence who gets what treatment.
Patients had to consent prior to randomization to be included in either of the two treatment arms, with some declining as they did not want to delay surgery. The overall resection rate was higher in the immediate surgery arm than in the CRT arm (72% versus 60%, P=0.065).
Borderline patients were "more or less" equally distributed, said van Tienhoven, but no data were presented describing which of these two groups derived the most benefit. Borderline resectable patients and even those considered to be resectable are not always able to go through with surgery, said van Tienhoven.
"Yet I must say that patients who chose to participate in the trial and who were randomized for the preoperative treatment, they were better off in the end," van Tienhoven said. He added that the notion that cancer must always be resected is changing, and that a lot surgeons tend to use neoadjuvant treatments.
"There's a fair possibility that this paradigm shift will continue based upon these results," he said.
Disclosures
van Tienhoven disclosed no relevant relationships with industry. Co-authors disclosed relevant relationships with Roche, ThermaSolutions, Merck Serono, Bayer, Amgen, and Nordic Bioscience.
Epstein disclosed no relevant relationships with industry.
Primary Source
American Society of Clinical Oncology
van Tienhoven G, et al "Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): A randomized, controlled, multicenter phase III trial" ASCO 2018; Abstract LBA4002.