Julien Taieb, MD

JULIEN TAIEB, MD, Professor of Medicine at Paris Descartes University in France, said the MODUL cohort was based on a clear rationale for adding atezolizumab (Tecentriq) to bevacizumab (Avastin) in the metastatic colorectal cancer setting. In immunodeficient mice, the combination of an anti–vascular endothelial growth factor (VEGF) agent and anti–programmed cell death protein 1 (PD-1) agent was shown to provide a high degree of tumor suppression, compared to either alone. And in hepatocellular carcinoma, a regimen of atezolizumab plus bevacizumab was shown to yield durable, ongoing responses in the majority of responders, he said.

“But here, despite activity in other immune-responsive tumor types, there was no improvement in progression-free or overall survival with the addition of atezolizumab to fluoropyrimidine and bevacizumab as first-line maintenance therapy in the population of patients with BRAF wild-type metastatic colorectal cancer,” he said. “Unfortunately, there was no efficacy at all, even in a subgroup.”

Studies that have combined anti–PD-1/programmed cell death ligand 1 agents with MEK inhibitors and VEGF inhibitors in microsatellite stable (MSS) cancers have failed, as have efforts to increase their treatment effects with chemotherapy, he pointed out. “My question now is whether we can really make a ‘cold’ tumor ‘hot,’” Dr. Taieb commented.

It is possible that using radiation therapy to induce abscopal effects may work in colorectal cancer, as it appears to in some other tumor types. Treatment effects might also be observed in MSS tumors selected for having high immunoscores or certain genetic characteristics. “I’m just not sure anymore,” he said.

“But we need to do something for patients with MSS disease, about 10% of whom do respond to immunotherapy, as the MODUL trial attempted to show,” Dr. Taieb said. “There was no signal of activity, but this does not mean there’s not a subgroup who will respond.” ■

DISCLOSURE: Dr. Taieb has received honoraria and fees for consulting/advising from Roche, Genentech, Lilly, Servier, Sanofi, Celgene, Shire, Amgen, Sirtex, Merck Serono, and MSD.