Dr. Harrison on the Effect of IO-Related Toxicities on Treatment Selection in RCC

Michael R. Harrison, MD, associate professor of medicine, member, Duke Cancer Institute, discusses common toxicities associated with immuno-oncology (IO)–based combinations and their effects on treatment selection in renal cell carcinoma (RCC).

Several key clinical trials in RCC can guide the selection of immunotherapy-based combinations in RCC, Harrison begins. These include the phase 3 CheckMate-9ER study (NCT03141177) of cabozantinib (Cabometyx) in combination with nivolumab (Opdivo), the phase 3 CLEAR study (NCT02811861) of lenvatinib (Lenvima) plus pembrolizumab (Keytruda), the phase 3 CheckMate-214 study (NCT02231749) of ipilimumab (Yervoy) plus nivolumab, and the phase 3 KEYNOTE-426 study (NCT02853331) of axitinib (Inlyta) combined with pembrolizumab.

Cross-analysis of patient characteristics, adverse effects (AEs), and efficacy in these trials is necessary to understand which patients may benefit from certain IO-based regimens, Harrison states.

In terms of patient characteristics, the proportion of favorable- vs poor-risk patients differed amongst these trials, he says. Factors affecting at-risk status include sarcomatoid features, prior nephrectomy, and liver metastasis. Moreover, high rates of dose reduction were observed with the use of cabozantinib and lenvatinib in the CheckMate-9ER and CLEAR trials. The immunotherapy component was stopped after 24 months of treatment in all trials, although some patients in CheckMate-214 were able to continue treatment for a longer period.

Although commonly experienced treatment-related AEs (TRAEs) should be factored into treatment selection, long-term TRAEs are difficult to decisively measure across trials, Harrison explains. Therefore, the selection of IO-based regimens should be guided by patient-reported quality of life (QOL) and an individual experience of toxicities, he emphasizes. QOL data from CheckMate-9ER are persuasive and show that patients receiving cabozantinib plus nivolumab have better QOLcompared with those receiving sunitinib (Sutent). This outcome was not observed with the other IO-TKI combinations, Harrison concludes.