Neoadjuvant chemoradiotherapy extends OS vs. upfront surgery in pancreatic cancer subsets
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Neoadjuvant gemcitabine-based chemoradiotherapy prolonged OS compared with upfront surgery among patients with resectable and borderline resectable pancreatic cancer, according to phase 3 study results in Journal of Clinical Oncology.
The optimal chemotherapy regimen for neoadjuvant treatment has not yet been established, but more effective regimens, including FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin), are available, researchers said.
“Neoadjuvant treatment was investigated in various phase 2 prospective trials with the hope that it might improve survival. Since the majority of patients already have occult metastasis at presentation, the aim of neoadjuvant treatment is to directly treat micrometastases and to improve the chance that patients receive the intended systemic treatment,” Eva Versteijne, MD, PhD, medical specialist in the department of radiation oncology at Cancer Center Amsterdam at University of Amsterdam, told Healio. “In addition, it is hypothesized that neoadjuvant treatment results in downstaging of the primary tumor, thereby improving the microscopically radical resection rate. Also, patients with very aggressive tumors not responding to neoadjuvant treatment could be spared futile surgery.”
Background and methodology
Versteijne and colleagues conducted the research because survival is poor for patients with pancreatic cancer who undergo standard treatment of upfront surgery followed by adjuvant therapy. Additionally, many patients do not receive adjuvant treatment because of complications or deterioration after surgery.
The investigator-initiated, nationwide, randomized PREOPANC trial included 246 patients with resectable or borderline resectable pancreatic cancer treated at 16 Dutch centers between April 24, 2013, and July 25, 2017. Researchers randomly assigned patients 1:1 to neoadjuvant chemotherapy (n = 119; median age, 66 years; interquartile range, 59-71; 54% men) or upfront surgery (n = 127; median age, 67 years; interquartile range, 60-73; 58% men).
In the chemotherapy group, Versteijne and colleagues administered three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle and, after restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. In the upfront surgery group, patients underwent surgery followed by six cycles of adjuvant gemcitabine.
OS served as the primary outcome.
Key findings
Results at median follow-up of 59 months showed longer OS for patients in the neoadjuvant chemoradiotherapy group compared with the upfront surgery group (median, 15.7 months vs. 14.3 months; HR = 0.73; 95% CI, 0.56-0.96). Researchers reported 5-year OS rates of 20.5% (95% CI, 14.2-29.8) with neoadjuvant chemotherapy vs. 6.5% (95% CI, 3.1-13.7) with upfront surgery. Additionally, neoadjuvant chemoradiotherapy demonstrated a consistent effect across the prespecified subgroups, including patients with resectable and borderline resectable pancreatic cancer.
“We had hoped for a survival benefit and were happily surprised to see that these outcomes were found in the long-term,” Versteijne said.
Implications
The PREOPANC trial has proved large, randomized controlled trials of neoadjuvant treatment in pancreatic cancer are possible with regard to recruitment, according to researchers. PREOPANC-2, which is comparing neoadjuvant gemcitabine-based chemoradiotherapy with neoadjuvant FOLFIRINOX, accrued 375 patients in less than 3 years.
In further research, Versteijne told Healio she would like to “investigate the role of newer chemotherapy, combined with stereotactic radiotherapy, to further improve outcomes of resectable and borderline resectable pancreatic cancer.”
For more information:
Eva Versteijne, MD, PhD, can be reached at Department of Radiation Oncology, Cancer Center Amsterdam, University of Amsterdam, P.O. Box 22660, 1105 AZ, Amsterdam, the Netherlands; email: e.versteijne@amsterdamumc.nl.
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