The ASCO Post interviewed Irvin M. Modlin, MD, Emeritus Professor of Gastroenterological Surgery, Yale University School of Medicine, regarding his thoughts on the NETTER-1 results and peptide receptor radionuclide therapies for neuroendocrine tumors. Dr. Modlin led the first study of a peptide receptor radionuclide therapy in the United States in 1990 and has done research in the field for more than 30 years.

Paradigm Change

Dr. Modlin sees Lu-177 dotatate as a true “paradigm change” in the treatment of neuroendocrine tumors—one that originated, interestingly, not in oncology but in nuclear medicine. He felt that it would provide the basis for a significant reconsideration of the current therapeutic paradigm for NET treatment.

“For practical purposes, you are seeing here, for the first time, a therapy that has an identifiable and accessible target prior to treatment, an agent that safely targets the tumor cell as opposed to obliterating a thousand adjacent normal cells, and a way to monitor response using molecular genomic parameters, which can assess treatment efficacy on an ongoing basis,” he explained.

He referred to new research, showing that certain circulating transcripts and gene clusters can predict and define the therapeutic efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors. This is a great advance over current methods of assessment, including imaging, which is not particularly sensitive in neuroendocrine tumors, and chromogranin A levels, which are in most instances 
“irrelevant” and often misleading, while providing little clinically useful information, according to Dr. Modlin.

As Dr. Modlin further explained in the interview, “When you measure 50 different genes in the blood, you get a real picture of what’s happening in the tumor, of whether the therapy is working or not. You can actually tell if a tumor is likely to be susceptible to treatment before you start [peptide receptor radionuclide therapy], and then while you are giving it, you have a molecular basis for knowing whether the tumor is decreasing, stabilizing, or progressing. It’s very novel work.”

Additional Comments From Milan and Denver

Lisa Bodei, MD, Deputy Director of the European Institute of Oncology, Milan, Italy, described such research at the 2016 Gastrointestinal Cancers Symposium. She reported that patients who respond to peptide receptor radionuclide therapy are observed to have significant reductions in neuroendocrine tumor transcripts, whereas nonresponders have elevated transcripts. Chromogranin A, on the other hand, was found to be noninformative. “Transcript analysis accurately defined diagnosis and response to [peptide receptor radionuclide therapy],” she said.

Dr. Bodei concluded, in her talk, that the integration of clinical, biologic, and genetic tumor as well as patient information appears to be “the logical and rational progression toward a personalized predictive assessment of the efficacy and tolerability” of this modality. “[Peptide receptor radionuclide therapy] appears to be the most predictive and effective neuroendocrine tumor therapy,” she maintained.

Eric Liu, MD, a neuroendocrine tumor specialist and surgeon at Rocky Mountain Cancer Center, Denver, Colorado, agreed with Dr. Modlin that peptide receptor radionuclide therapy could mean a big treatment advance in the field. “I’m very excited about this agent and very interested in the ways we will use it,” he said in an interview.

Dr. Liu cautioned that as a complex treatment, peptide receptor radionuclide therapy should be used under the auspices of “a multidisciplinary team, in the right patient, in the right setting, and at the right time.” ■

Disclosure: Dr. Bodei is a consultant for Ipsen and AAA. Drs. Modlin and Liu reported no potential conflicts of interest.