J. Randolph Hecht, MD, Professor of Clinical Medicine and Director of the Gastrointestinal Oncology Program at the University of California, Los Angeles, commented to The ASCO Post that it is premature to accept this algorithm in the absence of its correlation with clinical outcomes. The one dataset that correlated HER2 status with outcomes is the ToGA trial, which established the benefit of treating HER2-positive patients with trastuzumab.

“The data derived from ToGA was at least correlated with outcomes,” he noted.  “We need more datasets, and these will be coming out,” he said. One is the phase III TRIO-013 (LOGiC) trial of lapatinib, oxaliplatin, and capecitabine in locally advanced or metastatic HER2-amplified gastric cancer, for which Dr. Hecht is the principal investigator.

Explanation of Discordant Results Needed

What is confusing is that in breast cancer, FISH is known to be far more accurate than IHC in determining HER2 status, he pointed out. “That battle has been fought and won by FISH, which is the gold standard in breast cancer,” Dr. Hecht noted. “The question that comes up is, why this discordant result [with esophagogastric cancer in the ToGA trial]?”

Dr. Hecht said he would like to have assurance of the quality of the FISH assays in the study, and would like to know what the numerators and denominators are for the FISH ratio of 2.0 for positivity. “In many breast cancer trials, if there is loss of chromosome 17q so that the denominator is lower, you may not truly have amplification, which is required to affect the biology of the tumor. Maybe some of the IHC 0 to 1+ FISH-positive patients in the ToGA trial were false-positives, and this could explain some of the discordance.” In addition, Dr. Hecht is concerned about a screening strategy that may overtreat some patients with an expensive drug and exclude others from treatment with an active relatively nontoxic agent. ■

Disclosure: Dr. Hecht has received research funding from GlaxoSmithKline and Roche.