In the phase III GERCOR LAP07 trial reported by Pascal Hammel, MD, of Beaujon Hospital, Clichy, France, and colleagues in JAMA, there was no survival benefit of chemoradiotherapy vs continued chemotherapy in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib (Tarceva).1
In this open-label trial, 442 patients from 80 sites in France, Australia, New Zealand, Belgium, and Sweden were randomized between February 2008 and December 2011 to four monthly cycles of induction with gemcitabine at 1,000 mg/m2 weekly (n = 223) or gemcitabine plus erlotinib at 100 mg/d (n = 219). Patients without disease progression after 4 months underwent a second randomization to continue chemotherapy or to receive chemoradiotherapy consisting of radiotherapy at 54 Gy plus capecitabine for 2 months. During maintenance, the erlotinib dose was increased to 150 mg/d.
For the gemcitabine and gemcitabine/erlotinib groups in the first randomization, median age was 64 and 63 years, 52% and 51% were men, and nodal status was N0 in 60% and 57%, respectively. A total of 269 patients without disease progression at 4 months were randomized to continue chemotherapy (n = 136) or to undergo chemoradiotherapy (n = 133). Among these patients, median age was 63 and 62 years, 56% and 44% were men, and 58% and 57% had N0 nodal status.
Survival Outcomes
Study accrual was terminated early after interim analysis by the data and safety monitoring committee indicated that prespecified futility criteria were met. Median follow-up was 36.7 months. Median overall survival from first randomization was 16.5 months (95% confidence interval [CI] = 14.5–18.5 months) in the chemotherapy group vs 15.2 months (95% CI = 13.9–17.3 months) in the chemoradiotherapy group (hazard ratio [HR] = 1.03, P = .83). Median progression-free survival was 8.4 vs 9.9 months (HR = 0.78, P = .06). Locoregional progression was observed in 46% vs 32%, and metastatic progression was observed in 44% vs 60% of patients.
Median overall survival from first randomization was 13.6 months (95% CI = 12.3–15.3 months) among all 223 patients randomized to receive gemcitabine vs 11.9 months (95% CI = 10.4–13.5 months) among all 219 receiving gemcitabine/erlotinib (HR = 1.19, P = .09). There was also no significant difference in median progression-free survival (7.8 vs 6.5 months, HR = 1.12, P = .26).
Overall, chemotherapy, radiotherapy, or both were reintroduced in 190 patients (43%) after protocol completion. Median time to subsequent treatment was 6.1 months in the chemoradiotherapy group vs 3.7 months in the chemotherapy group (P = .02). Second-line chemotherapy consisted mostly of fluorouracil/platinum-based treatment and was balanced across the two groups.
Toxicity
During induction chemotherapy, the gemcitabine/erlotinib group had more frequent grade 3 or 4 anemia (P = .05), febrile neutropenia (P = .03), diarrhea (P = .006), and acneiform rash (P = .007). Among grade 3 or 4 adverse events, only nausea (6% vs 0%, P = .008) was more common with chemoradiotherapy vs chemotherapy.
The investigators concluded: “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.” ■
Disclosure: The study was supported by Roche and French National Institute of Cancer.For full disclosures of the study authors, visit jama.jamanetwork.com.
Reference
