TOPLINE:

Adding fluoropyrimidine-sensitized radiotherapy (CXRT) to adjuvant gemcitabine chemotherapy was not associated with improved overall survival or higher rates of grade 4/5 adverse events among patients with resected pancreatic head adenocarcinoma assessed in a phase 3 trial. However, in patients with node-negative disease, adding CXRT to chemotherapy was associated with significant improvements in both overall survival and disease-free survival.

METHODOLOGY:

• Given ongoing uncertainty about the role of adjuvant chemoradiotherapy after pancreatic cancer resection, researchers assessed whether adding CXRT to adjuvant gemcitabine could improve overall survival in this population.
• Researchers conducted a multicenter, randomized phase 3 trial in the US, Canada, Belgium, and Israel, enrolling patients who underwent curative-intent resection of pancreatic head adenocarcinoma.
• A total of 354 patients who completed five cycles of gemcitabine-based chemotherapy without progression were randomized 1:1 to receive either a sixth cycle of chemotherapy alone (174 patients) or a sixth cycle of chemotherapy followed by CXRT (180 patients).
• Patients randomized to CXRT received 50.4 Gy in 28 fractions targeting the postoperative tumor bed, gastrojejunostomy, and regional nodes, with concurrent continuous infusion 5-fluorouracil (5-FU) or oral capecitabine starting on day 1 of radiotherapy.
• Outcome measures included overall survival as the primary endpoint, measured from second-step randomization to death from any cause, and disease-free survival as a secondary endpoint. Median follow-up was 2.2 years for all patients and 7.4 years for surviving patients at final analysis in December 2023.

TAKEAWAY:

• Among the full cohort, adding CXRT was not associated with improved overall survival (hazard ratio [HR], 0.96; 90% CI, 0.79-1.18), with median overall survival of 31.1 months for chemotherapy alone and 27.3 months for chemotherapy plus CXRT.
• Adding CXRT was also not associated with a statistically significant improvement in disease-free survival, although median disease-free survival was numerically longer with CXRT (15.6 vs 12.4 months; HR, 0.82; 95% CI, 0.65-1.03).
• In a prespecified analysis, node-negative patients experienced significant improvements in overall survival (P = .0063) and disease-free survival (P = .014) with CXRT.
• Significantly more patients in the CXRT group experienced grade 3 adverse events (38% vs 19%; P < .001), primarily due to gastrointestinal toxicity and decreased lymphocyte counts, but grade 4/5 toxicity did not differ significantly (6% vs 5%; P = .68).

IN PRACTICE:

“These results, if confirmed in studies with current or future systemic therapies, would support the use of adjuvant/neoadjuvant CXRT for node-negative patients,” the study authors concluded.

SOURCE:

The study, led by Ross A. Abrams, MD, Rush University Medical Center, Chicago, was published online on June 9 in the Journal of Clinical Oncology.

LIMITATIONS: 

The study experienced slow accrual, requiring almost 9 years to achieve an adequate but lower than initially desired number of patients and overall survival events, which reduced statistical power from the planned 90% to 72% at the time of analysis. The choice of gemcitabine-based chemotherapy limits current applicability because FOLFIRINOX (folinic acid [leucovorin], 5-FU, irinotecan, oxaliplatin) or modified FOLFIRINOX has become the preferred adjuvant chemotherapy for patients able to tolerate it. Only 17% of patients had involved surgical margins, making it impossible to assess the potential radiotherapy benefit in margin-positive, node-negative patients due to insufficient sample size (only 10 total patients, five per arm). Interpreting nodal status in the neoadjuvant, postoperative setting is clinically difficult, which complicates the application of the node-negative benefit finding to current practice patterns that increasingly incorporate neoadjuvant therapy.

DISCLOSURES:

The study received support from the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology Statistics and Data Management Center), UG1CA189867 (NCORP), and preceding grants. The Radiation Therapy Oncology Group, now NRG Oncology, served as the sponsor of the studies analyzed in this manuscript. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.