Biomarkers May Identify Which Patients With Renal Cell Carcinoma Will Benefit From Nivolumab
Researchers at Johns Hopkins identified genes involved in tumor cell metabolism that may predict which patients with renal cell carcinoma are unlikely to respond to treatment with nivolumab.
Researchers identified potential biomarkers that may predict whether patients with renal cell carcinoma (RCC) are likely to respond to treatment with immunotherapeutics that target the anti-PD-1/PD-L1 pathway.1
In a retrospective study, researchers led by Suzanne Topalian, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, analyzed archived pretreatment tumor biopsies from 13 patients with metastatic RCC positive for PD-L1 who had gone on to receive the anti-PD-1 drug nivolumab. Four of the patients had responded to the treatment, and 9 had not.
Whole genome expression profiling showed that 110 genes were expressed at elevated levels in tumors from patients who did not respond to treatment with nivolumab. Further inspection revealed that these genes seemed to be functionally linked to tumor metabolism.
Those genes that were upregulated in tumors that were resistant to anti-PD-1 therapy are also expressed in cultured kidney cancer cell lines, the researchers found.
Tumors from patients who responded to treatment with nivolumab showed elevated levels of some genes that have immune functions.
“I think this study should be viewed as a launching point for more in-depth investigations,” said Dr Topalian in an interview with Cancer Therapy Advisor. “It shows a research approach that I think is going to be valuable not only in kidney cancer but other cancer types, where we are now seeing that anti-PD-1 drugs are having an impact.”
To date only 1 kind of biomarker, the PD-L1 immunohistochemistry (IHC) test, is approved for directing patient selection.
“The approved PD-L1 IHC tests can be helpful in guiding treatment, but they're not black and white tests,” said Dr Topalian. “I think we have still a lot of work to do in developing more predictive biomarkers for patients receiving anti-PD-1 and anti-PD-L1 therapies.”
Between 15 and 30 percent of patients with RCC have a durable response to anti-PD-1/PD-L1 therapies. Identifying predictive biomarkers can prevent those who are less likely to respond to treatment from unnecessarily enduring its potential adverse effects.
“We hope when people see this publication that they'll be interested enough that they may conduct more expansive trials, or that drug companies that are developing anti-PD-1 and anti-PD-L1 drugs for patients with kidney cancer may look at tumor specimens in their archives for the biomarkers we published here,” said Dr Topalian.
“The report that we published was from a single institution, Johns Hopkins, so by nature it's going to be somewhat limited in terms of patient numbers,” she said. “But again, we hope that by publishing the results this will generate interest and lead to future work in this area.”
- Ascierto ML, McMiller TL, Berger AE, et al. The intratumoral balance between metabolic and immunologic gene expression is associated with anti–PD-1 response in patients with renal cell carcinoma. Cancer Immunol Res. 2016 Aug 4. doi: 0.1158/2326-6066.CIR-16-0072 [Epub ahead of print]