Strategy to overcome tumors’ resistance to immunotherapy generates promising clinical trial results

Responses to immune checkpoint inhibitors improved after adding radiation therapy.

Date:November 18, 2021

Source:Massachusetts General Hospital

Summary:Immune checkpoint inhibitors strengthen the immune response against cancer cells, but the medications are ineffective against certain tumors. Results from a new clinical trial indicate that adding radiation may overcome this resistance to immune checkpoint inhibitors.

Excerpt from the Press Release:

Immune checkpoint inhibitors can boost the immune system’s response to tumor cells, but the medications tend to be ineffective against certain cancers, especially colorectal and pancreatic cancers. A new clinical trial led by investigators at Massachusetts General Hospital (MGH) indicates that combining radiation with immune checkpoint inhibitors may be an effective strategy to combat these resistant cancers.

Preclinical studies have shown that low-dose radiation can create a “tumor vaccine” environment that triggers an immune response when stimulated with the immune checkpoint inhibitors nivolumab and ipilimumab — which have different targets — in resistant cancers. As reported in Nature Cancer, researchers tested this strategy in a single-arm phase II trial of 40 patients with colorectal cancer and 25 patients with pancreatic cancer. In patients who received the planned treatment of radiation + nivolumab + ipilimumab, 37% of patients with colorectal cancer and 29% of patients with pancreatic cancer experienced responses to the therapy (with complete or partial responses or stable disease that did not progress).

“This is an impressive clinical result given that historically, these cancers respond in the low single digit percentage range,” says senior author David T. Ting, MD, associate clinical director for innovation at the MGH Cancer Center and an associate professor of medicine at Harvard Medical School. He added that new information indicates that improved timing of the sequencing of radiation therapy with immunotherapy may enhance efficacy that merits further investigation.

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