Expert Point of View: Axel Grothey, MD and Eric Van Cutsem, MD, PhD

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Two gastrointestinal cancer experts commented on the findings in interviews with The ASCO Post. Axel Grothey, MD, Professor of Oncology at the Mayo Clinic, Rochester, Minnesota, noted, “The PEAK and SPIRITT trial were decently designed, decently powered randomized phase II trials, and the results are surprisingly similar to what we expected. The data are interesting, and they suggest there is probably not a real difference between panitumumab [Vectibix] and bevacizumab [Avastin] in patients with KRAS wild-type disease. The definitive answers will come from phase III trials.” He said he would select the drugs based on patient profiles.

Eric Van Cutsem, MD, PhD, Professor at the University of Leuven in Belgium and Head of Digestive Oncology at University Hospital Gasthuisberg, added a note of caution. “Though these are important studies, they are randomized phase II trials and therefore not practice-changing.”

The two studies showed the drugs to be comparable “quantitatively,” he said, “but the benefit of each drug may be different for different patients. Some will benefit from panitumumab and some from bevacizumab. At this point, we have no way of selecting those patients. Biomarkers [also under investigation in these studies] will help us do that.”

He proposed that the EGFR ligands amphiregulin and epiregulin, and potentially BRAF and NRAS expression, may someday help identify patients best treated with EGFR inhibitors. “And patients who have low expression of these ligands or mutants for different genes may be better off with bevacizumab in this setting,” he suggested.

Drug Sequence Important

The sequence in which the two agents are applied is also important, he added. “We have data showing that bevacizumab is more active in early lines of treatment, and this is how I use it in most patients, but there are exceptions,” Dr. Van Cutsem said. “In KRAS wild-type patients where we want to go for a response and render the patient resectable, an anti-EGFR antibody usually gives a higher response upfront, though this was not seen in the PEAK trial.”

Dr. Van Cutsem elaborated on Dr. Grothey’s reference to the phase III comparisons and said they should be very informative as to the optimal use of the anti-EGFR and anti-VEGF agents in colorectal cancer. The German-Austrian FIRE trial has enrolled more than 900 patients for the comparison of cetuximab (Erbitux) and bevacizumab; results are expected at the 2013 ASCO Annual Meeting. The Cancer and Leukemia Group B (CALGB) is also comparing cetuximab and bevacizumab first-line, with overall survival as the primary endpoint, he said. In addition, he looks forward to seeing results of the biomarker analyses from the current phase II trials. ■

Disclosure: Dr. Grothey reported no potential conflicts of interest. Dr. Van Cutsem has received research funding paid to his institution by Amgen, Merck Serono, and Roche.

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