Chemoradiation May Convert Unresectable Pancreatic Cancers for Resection

"CRT improves the ratio of R0/R1/R2 resection in secondary surgery without increasing postsurgical mortality. Induction chemotherapy may enable biological selection of patients with a favorable prognosis who benefit the most from CRT," according to the study authors.

Chemotherapy plus chemoradiotherapy (CRT) did not improve the overall R0 resection rate or survival vs chemotherapy alone among those with unresectable pancreatic tumors, although the combination may facilitate R0 resection in surgically treated patients more often than chemotherapy alone, according to findings from the phase 3 CONKO-007 trial (NCT01827553) published in Journal of Clinical Oncology.1

Overall, 25.4% and 18.0% of patients in the chemotherapy/CRT and chemotherapy alone arms, respectively, underwent R0 resection, which reflected no statistically significant difference (P = .113). The rates of R1, R2, and no resection were 3.0%, 8.3%, and 63.3% in the chemotherapy/CRT group vs 10.2%, 7.8%, and 64.1% in the chemotherapy alone group (P = .03). Among patients who underwent surgery, CRT yielded significantly higher ratios of R0, R1, and R2 resections (P = .02); circumferential resection margin (CRM)–negative status rates (P = .04); and pathologic complete response (pCR) rates vs chemotherapy alone (P = .004).

Data showed a median overall survival (OS) of 14 months with chemotherapy alone vs 15 months with the addition of CRT, reflecting no significant difference in outcomes (HR, 0.94; 95% CI, 0.747-1.174; P = .57). Additionally, the median disease-free survival (DFS) was 8 months vs 9 months in each respective group (HR, 0.92; 95% CI, 0.736-1.156; P = .48).

Investigators noted that 122 of 336 patients in the intent-to-treat population underwent surgery, which correlated with superior survival (HR, 0.53; 95% CI, 0.408-0.676). The median survival was 19 months in patients with surgery vs 13 months in those without, with respective 5-year survival rates of 18.7% (95% CI, 11.1%-27.7%) vs 0% (P <.001). The median survival was 33 months in patients with a CRM-negative resection and 24 months in those with R0 resections, with respective 5-year survival rates of 30.4% (95% CI, 18.1%-51.1%) and 27.6% (95% CI, 17.4%-42.4%).

“In unresectable pancreatic cancer, induction chemotherapy followed by CRT is feasible, but not superior in survival to chemotherapy alone, instead shows the same rate of OS as chemotherapy alone. Secondary surgery is associated with a superior prognosis, especially if R0 is achieved,” lead study author Rainer Fietkau, MD, from the Department of Radiation Oncology at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) in Erlangen, Germany; the Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) in Erlangen, Germany; and the National Center for Tumor Diseases, wrote with coauthors in the publication.1 “CRT improves the ratio of R0/R1/R2 resection in secondary surgery without increasing postsurgical mortality. Induction chemotherapy may enable biological selection of patients with a favorable prognosis who benefit the most from CRT.”

Investigators of the CONKO-007 study assessed the value of CRT in the context of modern chemotherapy and surgery in 525 patients with unresectable tumors as part of a panel including 5 experienced surgeons. A total of 495 patients received induction chemotherapy consisting of fluorouracil plus irinotecan and oxaliplatin (FOLFIRINOX; n = 402) or gemcitabine (n = 93). After 336 patients showed no progression after 3 months of induction chemotherapy, investigators assigned this group to continue the same chemotherapy regimen (n = 167) or receive CRT at 50.4 Gy concurrently with gemcitabine (n = 169).

The trial’s primary end point was the overall R0 resection rate. Secondary end points included OS; DFS; locoregional control; toxicity; and comparators of all resection parameters, including R0, R1, R2, and no resection.

Patients 18 years and older with histologically confirmed adenocarcinoma of the pancreas, no evidence of distant metastasis in the thorax and abdomen, and no evidence of peritoneal carcinosis were eligible for enrollment on the trial.2 Other eligibility criteria included having an ECOG performance status of 0 to 2 and unresectable disease.

The median age was 64 years (range, 57-71) in the chemotherapy arm and 65 years (range, 57-71) in the CRT arm, and most patients in each group were male (55% vs 56%). Additionally, most in each respective arm had a WHO performance status of 0 (56% vs 62%), stage cT4 disease (64% vs 67%), grade 2 disease (33% vs 37%), and tumors localized in the head of the pancreas (64% vs 60%).

In the chemotherapy and CRT arms, respectively, investigators highlighted significant differences in the rates of grade 3/4 leukopenia (7% vs 30%; P >.001) and thrombocytopenia (8% vs 25%; P >.001). Three patients in the chemotherapy arm died due to toxicity, which included single instances of cytomegalovirus infection, pulmonary embolism, and peripheral arterial disease; no toxicity-related deaths occurred in the CRT arm.

References

1. Fietkau R, Ghadimi M, Grutzmann R, et al. Benefit of chemoradiotherapy versus chemotherapy after induction therapy for conversion of unresectable into resectable pancreatic cancer: the randomized CONKO-007 trial. J Clin Oncol. Published online August 13, 2025. doi:10.1200/JCO-24-01502
2. Pancreatic carcinoma: chemoradiation compared with chemotherapy alone after induction chemotherapy (CONKO-007). ClinicalTrials.gov. Updated April 11, 2024. Accessed August 15, 2025. https://tinyurl.com/au4nr2bc