An international phase 3 trial of patients with locally advanced, chemo-contained pancreatic cancer has found no significant difference in overall survival with chemoradiotherapy—a controversial treatment for this application—compared with chemotherapy alone.
The same study found no significant difference in overall survival with the drug gemcitabine compared with gemcitabine plus erlotinib (trade name Tarceva) used as maintenance therapy.
JAMA published the findings online May 3.
Pascal Hammel, MD, PhD, of Beaujon Hospital in France and colleagues drew from the LAP07 study, an unblinded randomized trial conducted by the French-led European Cooperative group GERCOR.
Homing in on patients with locally advanced pancreatic cancer controlled after four months of gemcitabine-based induction chemotherapy, the researchers analyzed two randomizations.
One compared 223 patients who received 1,000 mg/m2 weekly of gemcitabine alone with 219 patients who received 1000 mg/m2 of gemcitabine plus 100 mg/d of erlotinib.
The other compared 136 patients who received randomized chemotherapy with 133 patients who underwent chemoradiotherapy (54 Gy plus capecitabine).
The team’s key findings:
- With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months and chemoradiotherapy at 15.2 months (hazard ratio, 1.03).
- Median overall survival from the date of the randomization for the 223 patients receiving gemcitabine was 13.6 months and 11.9 months for the 219 patients receiving gemcitabine plus erlotinib (hazard ratio, 1.19; 188 deaths vs. 191 deaths).
Meanwhile, chemoradiotherapy was associated with marginally superior local control (32 percent vs. 46 percent) and no increase in grade 3 to 4 toxicity, except for nausea.
The lack of superiority of chemoradiotherapy “cannot be explained by insufficient power of the study,” the authors write in their discussion. “The trial was stopped after the independent data monitoring committee concluded that the planned intermediate analysis could be the final one to answer the primary objective of the study. Quality of radiation therapy could be questioned because deviations from the protocol can impact negatively on the outcome” of patients receiving chemoradiotherapy.
“Although LAP07 [previously] confirmed the safety of radiation therapy with concurrent capecitabine,” they add, “a further intensification of the chemoradiotherapy regimen seems to be needed.”
In accompanying commentary, Deborah Schrag, MD, MPH, of the Dana Farber Cancer Institute in Boston predicts that proponents of chemoradiation will find reasons to perpetuate its use despite the “clear negative result” previously shown from the LAP07 trial.
Such proponents “will note that deviations from optimal radiation technique could have compromised efficacy,” she writes. “However, most protocol violations were minor and adherence appears to have been more carefully monitored than in prior trials.”
Schrag further states, “advocates of chemoradiation will note that, even though the [Hammel] study does not demonstrate superiority for chemoradiation, it also does not demonstrate superiority for chemotherapy, with near identical outcomes between treatments.”
“Ideally, future pancreatic cancer trials will identify molecular markers that better predict responsiveness to specific treatments including radiation and will allow for more focused approaches to treatment selection,” Schrag concludes. “In the meantime, chemoradiation need not constitute an essential component of the therapeutic backbone.”