Newly Discovered Biomarkers Suggest Who May Benefit From Liver Cancer Treatment

Researchers at Roswell Park Comprehensive Cancer Center found a biomarker that may help to determine which patients with hepatocellular carcinoma will respond to treatment with Nexavar, leading to more individualized treatment options.
BY Kristie L. Kahl
PUBLISHED September 17, 2019
Researchers at Roswell Park Comprehensive Cancer Center found a biomarker that may help to determine which patients with hepatocellular carcinoma (HCC) will respond to treatment with Nexavar (sorafenib), which could lead to more individualized treatment options and better overall outcomes for those diagnosed with the disease.

“Only recently, in the last two or three years, we've gotten five or six more drugs to treat liver cancer. And so when you have the options, you want to know which patients are going to benefit from the one you've always had, and which patients you may want to consider something else or consider a combination therapy,” explained study investigator Dr. Renuka Iyer, section chief for gastrointestinal oncology at Roswell Park. “So, I think that is kind of the big driver. And when (a patient has) limited liver function, you want to pick your poison carefully.”

HCC, the most common type of liver cancer, is typically treated with the oral chemotherapy Nexavar. However, side effects from this drug may cause many patients to miss doses or discontinue treatment.

“If (an oncologist) could know ahead of time by looking at specific biomarkers in a patient before they started therapy, knew that there was a good chance that they were going to respond to therapy, then it gives the clinician a tool to encourage these patients to stay on treatment, even if there is those interruptions, because then we are saying that they are going to, despite the side effects, never going to benefit in terms of their clinical survival from this therapy. So that would be, in my opinion, a quality of life issue,” study investigator Dr. Yasmin Thanavala, a scientist in the Department of Immunology and Roswell Park, said in an interview with CURE.

Therefore, in the four-year study, the researchers collected blood samples from 30 patients both before treatment and at two timepoints during treatment with Nexavar. They found that patients with elevated levels of a subset of CD8+ cytotoxic T-cells (cells they kill cancer cells) had better outcomes, as well as those whose tumors expressed a high ratio of CD4+ T-effector/T-regulatory cells prior to treatment.

In addition, they found that a decreased amount of PD-1 and CTLA-1 protein expressions in patients’ tumors could suggest combination treatment should be used, like Nexavar and a checkpoint inhibitor such as Opdivo (nivolumab).

These findings are important for patients, giving them the confidence to stay om or start back up on treatment with Nexavar if their tumors express these biomarkers, Iyer said. “The toxicity of these therapies are not trivial and knowing ahead of time that the person is going to benefit allows us to keep them on the medicine that is going to prolong their lives,” she added.

“In addition, I think the big advantage for patients is the confidence that the likelihood of this is not just average – a much larger proportion of patients will benefit. And I think that confidence allows them to make better decisions with their life, especially given that this is not a curable disease.”

Lastly, she recommends for more patients to join clinical trials like that so that researchers can continue to advance treatment options for those with HCC. “(We’ve made) a lot of progress in liver cancer because of the patients participating and taking a chance, allowing us to learn,” Iyer said. “(Participating in clinical trials) is something we always want patients to consider whenever they have the opportunity and if it's right for them.”
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