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Expert Point of View: Jordan Berlin, MD


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Jordan Berlin, MD

Jordan Berlin, MD

Jordan Berlin, MD, the Ingram Professor of Cancer Research and Professor of Medicine at Vanderbilt University Medical Center, Nashville, discussed the FOxTROT study at the oral session.

“FOxTROT did reach its targeted hazard ratio, but the bottom line is the P value did not quite make it to where it was supposed to be,” Dr. Berlin said. Although the results are “not definitive in terms of efficacy,” and are not yet practice-changing, he noted, the study points the way to neoadjuvant chemotherapy as a reasonable treatment option. Having the data to show neoadjuvant therapy is safe, added Dr. Berlin, “means that medical oncologists can go first…. We don’t always have to be at the end of treatment.”

Its effect on preventing relapse aside, the FOxTROT trial showed that neoadjuvant therapy with FOLFOX (fluorouracil, leucovorin, oxaliplatin) before surgery is feasible and safe; it also appears to increase the likelihood that patients will receive at least one dose of chemotherapy to treat micrometastatic disease. In fact, the data drove home the fact, he said, “that a lot of patients may not make it to postoperative adjuvant therapy in a timely manner.”

Neoadjuvant therapy did not increase the operative complication rate and, in fact, actually seemed to be better in this regard. “So, we seem to have helped the surgeons,” said Dr. Berlin.

Perhaps its only downside is the risk of overtreatment of early-stage disease, he suggested. The postoperative chemotherapy arm included patients with stage I disease (4%) and stage 2 disease (45%), “and we know that most patients with stage 2 disease do not need adjuvant therapy,” he pointed out.

MMR Deficiency and Neoadjuvant Therapy

Dr. Berlin found the exploratory analysis to be interesting, suggesting that patients with mismatch repair (MMR)-deficient tumors did not benefit from neoadjuvant therapy. Prior studies have shown that patients who had stage 2 MMR-deficient tumors did not benefit from adjuvant fluoropyrimidine-based regimens, but the same was not true for patients with stage 3 MMR-deficient tumors.

“There’s a lot we don’t understand about patients with colon cancer, and they seem to be different at each stage of the disease,” said Dr. Berlin. “I agree with the authors that little can be derived from this intriguing exploratory analysis, except perhaps that patients with MMR-deficient tumors need to have their own adjuvant studies.”

With data such as FOxTROT supporting neoadjuvant chemotherapy, Dr. Berlin suggested that future clinical trials should consider including a neoadjuvant arm. 

DISCLOSURE: Dr. Berlin has served as a consultant or advisor for AbbVie, Arno Therapeutics, AstraZeneca, Bayer Health, BeiGene, Celgene, Cornerstone Pharmaceuticals, Eisai, EMD Serono (unpaid), Erytech Pharma, Exelixis, Five Prime Therapeutics, Genentech/Roche, Gritstone Oncology, Karyopharm Therapeutics, LSK Biopharma, Rafael, Seattle Genetics, and Taiho and has received honoraria from Nestle Health Science. He has received institutional research funding from AbbVie, Bayer, Boston Biomedical, EMD Serono, Five Prime, Genentech/Roche, Immunomedics, Incyte, Lilly, Loxo, Macrogenics, Novartis (Array), Pharmacyclics, PsiOxus, Symphogen, and Taiho.


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