Dr. Choueiri on Checkpoint Inhibitor/TKI Combinations in RCC

Toni Choueiri, MD
Published: Wednesday, Nov 21, 2018



Toni Choueiri, MD, director, Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, Jerome and Nancy Kohlberg Associate Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses combinations of checkpoint inhibitors and TKIs for the treatment of renal cell carcinoma (RCC).

Checkpoint inhibitors such as nivolumab (Opdivo) and TKIs such as sunitinib (Sutent) have shown promise as monotherapy in the treatment of advanced RCC. Now, there is significant interest ongoing exploring these mechanisms of action in combination, says Choueiri. There are enough phase I data to suggest that these combinations will be taken to the next stage of research.

The biggest challenge with combining these therapies is the management of adverse events (AEs), he adds. Checkpoint inhibitors and targeted therapies each have their own unique toxicity profile requiring different methods of treatment. For example, pneumonitis is an AE associated with immunotherapy, but it is not seen with TKIs.

Diarrhea is an AE that can be experienced with either therapy, but management of this event will differ depending on the therapy. For example, if the diarrhea is immune-mediated, physicians would treat with steroids, but if the diarrhea results from TKI treatment, it is grounds to discontinue therapy, Choueiri says.
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Toni Choueiri, MD, director, Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, Jerome and Nancy Kohlberg Associate Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses combinations of checkpoint inhibitors and TKIs for the treatment of renal cell carcinoma (RCC).

Checkpoint inhibitors such as nivolumab (Opdivo) and TKIs such as sunitinib (Sutent) have shown promise as monotherapy in the treatment of advanced RCC. Now, there is significant interest ongoing exploring these mechanisms of action in combination, says Choueiri. There are enough phase I data to suggest that these combinations will be taken to the next stage of research.

The biggest challenge with combining these therapies is the management of adverse events (AEs), he adds. Checkpoint inhibitors and targeted therapies each have their own unique toxicity profile requiring different methods of treatment. For example, pneumonitis is an AE associated with immunotherapy, but it is not seen with TKIs.

Diarrhea is an AE that can be experienced with either therapy, but management of this event will differ depending on the therapy. For example, if the diarrhea is immune-mediated, physicians would treat with steroids, but if the diarrhea results from TKI treatment, it is grounds to discontinue therapy, Choueiri says.



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