• Oncology Clinical Trials
• Gastrointestinal Cancers

• Oncology Clinical Trials
• Gastrointestinal Cancers
• Oncology

Chemoradiotherapy (CRT) is not superior to chemotherapy and the addition of erlotinib provides no benefit in the treatment of locally advanced pancreatic cancer (LAPC). Pascal Hammel, MD, PhD, Hôpital Beaujon, Clichy, France, presented data from the Randomized Multicenter Phase 3 Study in Patients With Locally Advanced Adenocarcinoma of the Pancreas [LAP07; NCT00634725; Hammel P et al. J Clin Oncol 2013 (suppl; abstr LBA4003)].

Although not metastatic, LAPC is nonresectable due to the involvement of the superior mesenteric artery and the celiac trunk with tumor. Overall survival (OS) of LAPC is 9 to 12 months, which is greater than that of metastatic pancreatic cancer; however, the treatment of LAPC, including the role of CRT is controversial. The primary objective of the LAP07 study was to determine if CRT improved OS in patients whose disease was controlled following 4 months of induction chemotherapy.

In the international Phase 3 LAP07 study, 442 patients with LAPC and a performance status of 0 to 2 were first randomized to receive gemcitabine (n=223) or gemcitabine plus erlotinib 100 mg/day (n=219) for 4 months. Of the 442 patients, 269 patients (61%) with controlled disease were able to undergo a second randomization to receive 2 additional months of gemcitabine or 54 Gy of CRT plus 1600 mg/m² of daily capecitabine. Erlotinib (150 mg/day) was continued as maintenance therapy in patients that had received it during the first randomization.

The median follow-up was 36 months and included 221 deaths, which allowed the interim analysis to be adequately powered. The primary endpoint was OS following the second randomization. The effect of erlotinib on OS, tolerance of treatment, predictive markers, and presence of circulating tumor cells were secondary endpoints.

In the LAP07 study, CRT was demonstrated not to be superior to chemotherapy in the treatment of LAPC. In the chemotherapy arm, OS was 16.4 months, compared with 15.2 months in the CRT arm (HR, 1.03; 95% CI, 0.79 to 1.34; p=0.8295). Following the first randomization, there was a trend for decreased OS in the gemcitabine plus erlotinib arm at 11.9 months compared with the gemcitabine arm at 13.6 months (HR, 1.19; 95% CI, 0.97 to 1.45; p=0.093); however, this result was not statistically significant.

Following the first randomization, a greater number of patients experienced adverse events such as decreased hemoglobin, febrile neutropenia, diarrhea, and acneiform rash in the gemcitabine plus erlotinib arm, compared with the gemcitabine arm. Following the second randomization, both treatment regimens were well tolerated with a similar frequency of adverse events except for an increase in the number of patients that experienced nausea in the CRT arm (0 vs 6 patients; p=0.009).

Dr. Hammel stated that, in his opinion, the data from the LAP07 trial suggest that the standard of care for the treatment of LAPC should be chemotherapy, with CRT reserved for use as an option if the disease is controlled by chemotherapy. Although CRT or erlotinib provided no additional advantage to patients in the present study, there may be a subset of patients that could benefit, which is currently under investigation.

• © 2013 MD Conference Express®