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Original Investigation
May 3, 2016

Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial

Author Affiliations
  • 1Department of Digestive Oncology, Beaujon Hospital (AP-HP), Clichy, France
  • 2Department of Radiotherapy, Tenon Hospital (AP-HP), Paris, France
  • 3Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium
  • 4Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia
  • 5Australasian Gastrointestinal Trials Group (AGITG), Camperdown, Australia
  • 6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
  • 7Department of Radiology, Oncology, and Radiation Science, University of Uppsala, Uppsala, Sweden
  • 8Department of Gastroenterology, Jean Mermoz Hospital, Lyon, France
  • 9Department of Gastroenterology, Saint-Luc University Clinics, Brussels, Belgium
  • 10Department of Gastroenterology, Robert Debré Hospital, Reims, France
  • 11Department of Medical Oncology, Nepean Hospital NSW, Sydney, Australia
  • 12Department of Medical Oncology, Saint-Antoine Hospital (AP-HP), Paris, France
  • 13Department of Radiotherapy and Medical Oncology, Sainte-Catherine Institute, Avignon, France
  • 14Department of Medical Oncology, Franco-British Hospital Institute, Levallois-Perret, France
  • 15Oncology Multidisciplinary Research Group (GERCOR), Paris, France
  • 16Department of Methodology and Quality of Life in Oncology, Hospital Minjoz, Besançon, France
  • 17Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France
JAMA. 2016;315(17):1844-1853. doi:10.1001/jama.2016.4324
Abstract

Importance  In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown.

Objectives  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.

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.

Interventions  In the first randomization, 223 patients received 1000 mg/m2 weekly of gemcitabine alone and 219 patients received 1000 mg/m2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine).

Main Outcomes and Measures  The primary outcome was 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 (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. 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 (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 decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea.

Conclusions and Relevance  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 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.

Trial Registration  clinicaltrials.gov Identifier: NCT00634725

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