Cancer Trials Boost Immunotherapies

"Cancer researchers and drugmakers are beginning to broaden the benefits of so-called immunotherapies by zeroing in on patient or tumor characteristics to better predict who might respond to the powerful treatments.

In research presented at a scientific meeting this week, oncologists made early but promising inroads into various cancers with immunotherapy drugs from GSK PLC, Bristol-Myers Squibb Co. and others that harness the power of the immune system to fight cancer with generally fewer side effects than other therapies.

The drugs tend to work in a fraction of patients. Researchers are scouring common traits in some patients' biology that could help anticipate how well they might respond to certain therapies, in the hope that such precision might improve treatment options for patients and avenues for future research.

In one example, researchers at Memorial Sloan Kettering Cancer Center in New York treated 18 patients with an immunotherapy drug made by GSK based on the rare genetic makeup of their tumors. All the participants went into remission for months or longer without surgery, chemotherapy or radiation and haven't yet seen their cancers return. Some have been in remission for two years.

"That's really what you call personalized immunotherapy at its best," said Roy Herbst, deputy director of the Yale Cancer Center, who wasn't involved in the rectal-cancer study presented at the American Society for Clinical Oncology's annual meeting in Chicago.

Dr. Herbst is a lead researcher on a National Cancer Institute trial that is using genetic sequencing to attempt to match advanced lung-cancer patients with new therapies at some 700 sites across the U.S.

"I'm curing people now with immunotherapy, but only two out of 10," Dr. Herbst said. "I'm trying to get to all 10."

Immunotherapies have transformed treatment in particular for some advanced cancers including melanoma, lung cancer and blood cancers. World-wide sales for immuno-oncology drugs reached $40 billion in 2021 and are projected to grow, according to market-research firm EvaluatePharma. Oncology is a leading area of research investment for pharmaceutical companies, and many have pivoted to cancer research from other areas.

Despite the progress and investments, immunotherapies have worked inconsistently across cancers and patients. Overall, oncologists estimate that the response rate is around 20% across cancer types. The drugs can wipe out cancer for some people but fail to work for others, subjecting them to costs and side effects without restraining their disease.

"This is the field's biggest challenge, to identify which patients respond to which immunotherapies," said Robert Vonderheide, director of the Abramson Cancer Center at the University of Pennsylvania.

Some biological indicators, such as levels of a protein on cancer cells called PD-L1, already help clinicians select treatments [1]. Researchers are scouring specific tumor mutations, a person's individual immune response and even the microorganisms in their bodies to find more signals, or biomarkers, that can hint at who is most likely to benefit.

The Food and Drug Administration has approved some immunotherapies for patients that have specific biomarkers. One such drug is GSK's Jemperli, or dostarlimab, which is approved for patients with recurrent or advanced endometrial cancer or solid tumors that have a genetic abnormality called mismatch-repair deficiency, or dMMR.” [2]

1. "PD-L1 is a protein that acts as a kind of “brake” to keep the body’s immune responses under control. PD-L1 may be found on some normal cells and in higher-than-normal amounts on some types of cancer cells. When PD-L1 binds to another protein called PD-1 (a protein found on T cells), it keeps T cells from killing the PD-L1-containing cells, including the cancer cells. Anticancer drugs called immune checkpoint inhibitors bind to PD-L1 and block its binding to PD-1. This releases the “brakes” on the immune system and leaves T cells free to kill cancer cells."

2.  U.S. News: Cancer Trials Boost Immunotherapies
Abbott, Brianna. 
Wall Street Journal, Eastern edition; New York, N.Y. [New York, N.Y]. 10 June 2022: A.3.