In a study published in JAMA, Pascal Hammel, M.D., of Beaujon Hospital, France, and colleagues assessed if chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer.

In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial, and the efficacy of erlotinib is unknown. The objective was to assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival.

For this study, the researchers first randomly assigned 449 patients to receive gemcitabine alone (n = 223), and 219 patients received gemcitabine plus erlotinib.

In the second randomization involving patients with the progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy, and 133 underwent chemoradiotherapy (54 Gy [a measure of radiation dose] plus the chemotherapy drug capecitabine).

Design, Setting, and Participants

In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013. Gemcitabine at a dose of 1000 mg/m2 was delivered as a 30-minute intravenous infusion weekly for 3 weeks, followed by a 1-week rest (1 cycle), for 4 cycles. Erlotinib was given once-daily orally at a dose of 100 mg. During the maintenance phase, the daily dose of erlotinib was increased to 150 mg.

Outcomes

The primary outcome was an overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects.

Results

A total of 442 of the 449 patients enrolled underwent the first randomization. Of these, 269 underwent the second randomization.  With a median follow-up of 36.7 months.

The median overall survival was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). 

Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths).

Chemoradiotherapy was associated with the decreased local progression (32% vs. 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea.

In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival.

Although with chemoradiotherapy compared with chemotherapy alone, and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy.

The lack of superiority of chemoradiotherapy cannot be explained by the insufficient power of the study. 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.