Claire F. Verschraegen, MD, professor of medicine, director of the Division of Medical Oncology, the Ohio State University College of Medicine, Diane Nye and Michael Rayden chair in Innovative Cancer Research, director for translational research, the Ohio State University Comprehensive Cancer Center (OSUCCC) – James, discusses adverse effects (AE) that are commonly associated with the use of single-agent nivolumab (Opdivo) vs the combination of ipilimumab (Yervoy) plus nivolumab in melanoma.

Most patients who receive single-agent nivolumab also experience any-grade AEs, according to Verschraegen. These can range from low-grade, temporary fatigue to chronic autoimmune thyroiditis, Verschraegen begins. The latter toxicity can impact thyroxine, a thyroid hormone that regulates metabolic rate, digestion, heart and muscle function, brain development, and bone health. Notably, a significant decrease in thyroxine levels may require these patients to go on hormone replacement therapy, Verschraegen states.

Similarly, single-agent nivolumab can decrease the secretion of steroids and insulin, leading to hyperglycemia. However, it is rare that this insulin deficiency can trigger the development of new-onset type I diabetes, Verschraegen adds.

Compared with single-agent immunotherapy, the ipilimumab and nivolumab doublet is associated with a higher chance of experiencing toxicities, Verschraegen continues. The risk of severe grade 3 or 4 AEs is particularly pronounced, and increases from about 16% with the single agent to 55% with the doublet, she says. Grade 3 or 4 AEs can necessitate hospitalization or a trip to the emergency room. In this situation, patients would require rapid interventions, Verschraegen explains. Overall, the types of toxicities observed with combination or single-agent immunotherapy are the same, but the risk of chronic AEs does increase with immunotherapy doublets, Verschraegen states.

Although chronic AEs can affect quality of life (QOL) for patients receiving immunotherapy, recent data have shown an improvement in the rate of complete remissions achieved with these classes of drugs , Verschraegen notes. Future investigation is required to determine which AEs could be reversed or better mitigated, as this could improve QOL, Verschraegen concludes.

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Claire F. Verschraegen, MD, discusses adverse effects that are commonly associated with the use of single-agent nivolumab vs the combination of ipilimumab plus nivolumab in melanoma.


Dr Verschraegen on Toxicities Associated with Single-agent vs Doublet Immunotherapy in Melanoma

Claire F. Verschraegen, MD, professor of Medicine, director of the Division of Medical Oncology, the Ohio State University College of Medicine, Diane Nye and Michael Rayden chair in Innovative Cancer Research, director for translational research, the Ohio State University Comprehensive Cancer Center (OSUCCC)–James, discusses the need for predictive biomarkers for the use of immunotherapy in the treatment of melanoma.

No predictive biomarkers are currently known that could help determine which patients with melanoma would best respond to immunotherapy, Verschraegen says. Although tumor mutational burden and PD-L1 expression can be measured, there is no helpful correlation between these factors and how patients will respond, according to Verschraegen, who adds that patients with no biomarkers can still respond to immunotherapy, Verschraegen adds.

Frontline immunotherapy remains the standard of care for patients with melanoma. However, consulting with individual patients remains important to determine the best course of treatment, Verschraegen concludes.

Claire F. Verschraegen, MD, discusses the need for predictive biomarkers for the use of immunotherapy in the treatment of melanoma.


Dr. Verschraegen on the Need for Predictive Biomarkers for Immunotherapy in Melanoma

Claire F. Verschraegen, MD, professor of Medicine, director of the Division of Medical Oncology, the Ohio State University College of Medicine, Diane Nye and Michael Rayden chair in Innovative Cancer Research, director for translational research, the Ohio State University Comprehensive Cancer Center (OSUCCC)– James, discusses the need to improve the management of treatment-related adverse effects (TRAEs) of immunotherapy in melanoma.

As the use of immunotherapy has become commonplace in the treatment of melanoma, there remains a need to address TRAEs that arise, Verschraegen says. Quick intervention is key to prevent long-term disability that can stem from TRAEs, Verschraegen continues.

Future trials in melanoma must focus on the management of immunotherapy-based TRAEs, Verschraegen explains. Additionally, research into the topic has already begun at the OSUCCC– James, Verschraegen notes. The use of immunotherapy in melanoma is creating a new field of pathologies that need to be better understood, defined, and treated, Verschraegen concludes.

Claire F. Verschraegen, MD, discusses the need to improve the management of treatment-related adverse effects of immunotherapy in melanoma.

Dr. Verschraegen on the Need to Address TRAEs of Immunotherapy in Melanoma

Claire Verschraegen, MD, professor of medical oncology, University of Vermont Cancer Center, discussing combining avelumab (Bavencio) with other immunotherapy agents for patients with lung cancer.

Avelumab is different from pembrolizumab (Keytruda) or nivolumab (Opdivo) because it is a PD-L1 monoclonal antibody. Therefore, combining these agents can potentially create a higher benefit for patients.

Dr. Verschraegen on Combining Immunotherapy Agents in Lung Cancer

Claire Verschraegen, MD, professor of Medical Oncology, University of Vermont Cancer Center, discusses the results of the JAVELIN Solid Tumor trial during an interview at the IASLC 17th World Conference on Lung Cancer in Vienna, Austria.

JAVELIN Solid Tumor is an ongoing, multicenter phase I study exploring avelumab in multiple solid tumor types. The agent is a fully human IgG1 monoclonal antibody that blocks the PD-1/PD-L1 interaction but leaves PD-L2 signaling intact, which allows antibody-dependent cellular cytotoxicity to contribute to antitumor activity.

Patients with advanced NSCLC, who had not previously been treated systemically for metastatic or recurrent disease, and who did not have an activating EGFR mutation or ALK rearrangement, and were not preselected for PD-L1 expression, received avelumab 10 mg/kg IV over 1 hour every 2 weeks until progression, unacceptable toxicity, or withdrawal from the trial.

The results showed that first-line avelumab monotherapy demonstrated clinical activity, and the agent was well-tolerated in these patients. A phase III trial comparing avelumab with platinum-doublet in first-line NSCLC is currently in progress, says Verschraegen.

View more from the IASLC 17th World Conference on Lung Cancer

Claire Verschraegen, MD

Articles

Dr Verschraegen on Toxicities Associated with Single-agent vs Doublet Immunotherapy in Melanoma

Dr. Verschraegen on the Need for Predictive Biomarkers for Immunotherapy in Melanoma

Dr. Verschraegen on the Need to Address TRAEs of Immunotherapy in Melanoma

Dr. Verschraegen on Combining Immunotherapy Agents in Lung Cancer

Dr. Verschraegen on the JAVELIN Solid Tumor Trial in Advanced NSCLC