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TOPLINE: 

A phase 3 trial found that adding chemoradiotherapy (CRT) after induction chemotherapy in patients with unresectable pancreatic cancer did not extend overall survival compared to chemotherapy alone but did increase the R0 resection rate among patients who underwent surgery. Although no overall survival difference was observed between treatment arms, those who received surgery had longer overall survival.

METHODOLOGY:

• Chemotherapy is standard of care for locally advanced pancreatic cancer, but few patients survive 5 years. The benefit of additional local therapy, including radiotherapy or surgery, remains uncertain.
• Researchers conducted a phase 3 randomized clinical trial (CONKO-007) involving 525 patients with histologically confirmed unresectable pancreatic cancer. Of these, 495 received induction chemotherapy (402 with fluorouracil, irinotecan, and oxaliplatin [FOLFIRINOX] and 93 with gemcitabine). A total of 336 patients who did not experience disease progression were randomly assigned to either continue chemotherapy (n = 167) or receive CRT (n = 169).
• Patients in the CRT arm received 50.4 Gy of radiation in 28 fractions concurrently with weekly gemcitabine (300 mg/m²), followed by three weekly doses of gemcitabine 1000 mg/m².
• Initially, the primary endpoint was overall survival, but due to slow enrollment and the observation that patients often achieved resectability, that endpoint was changed to R0 resection rate (no tumor cells detectable at the resection margin on histopathologic examination) in the randomly assigned population. The median follow-up was 76 months.
• A panel of experienced surgeons centrally assessed resectability before and after treatment and recommended surgery if tumors were deemed resectable.

TAKEAWAY:

• Surgery was performed at similar rates in both arms (36.6% after CRT and 35.9% after chemotherapy). Among patients who underwent surgery, the R0 resection rate was significantly higher after CRT (69% vs 50%; P = .04). However, in the overall cohort, the R0 resection rate did not differ significantly between the CRT and chemotherapy arms (25% vs 18%; P = .113).
• Similarly, patients who received surgery had significantly better overall survival (hazard ratio [HR], 0.53; P < .001). Median survival was 19 months with surgery vs 13 months without (5-year survival, 18.7% vs 0%; P < .001). However, overall survival did not significantly differ between the CRT and chemotherapy arms (median, 15 months vs 14 months; HR, 0.94; P = .57).
• The ratios of R0/R1/R2 resection, circumferential resection margin-negative status, and pathologic complete response rate were significantly higher with CRT.
• Toxicities were largely comparable in the two arms; however, rates of grade 3 and 4 leukopenia and thrombocytopenia were higher with CRT.

IN PRACTICE:

“Although not improving overall R0 resection rate or survival, CRT enables R0 resection in surgically treated patients more often than chemotherapy alone,” the authors wrote. 

SOURCE:

The study, led by Rainer Fietkau, MD, of Friedrich-Alexander-Universität Erlangen-Nürnberg in Erlangen, Germany, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

The primary study endpoint was changed, which may result in a change in type I error. The knowledge that R0 resection may improve outcomes might have influenced treating physicians’ behavior. Financial constraints prevented central review of radiation delivery. Although resectability was assessed both locally and by a central tumor board, noninvolved surgeons might have classified some cases differently, as borderline resectable. 

DISCLOSURES:

The study received support from German Cancer Aid (Deutsche Krebshilfe 109284). Some authors declared receiving research funding or honoraria and having other ties with various sources.