Dr Tan on Important Considerations for Nivolumab/Ipilimumab Selection in Metastatic ccRCC

“What we showed was that we didn’t meet our primary end point yet. We’re showing what the outcomes are after the first 3 months of induction treatment with ipilimumab and nivolumab. What we learned here is this is a different type of [patient] population than CheckMate 214, even though the inclusion and exclusion criteria were relatively similar.”

Alan Tan, MD, associate professor of medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center and genitourinary oncology and melanoma specialist at Vanderbilt-Ingram Cancer Center, emphasized the importance of considering nuances in patient populations, as well as the relative safety profiles of immune-oncology (IO) vs IO/TKI regimens , before choosing ipilimumab (Yervoy) plus nivolumab (Opdivo) as treatment for patients with metastatic clear cell renal cell carcinoma (ccRCC).

The phase 3 PDIGREE (Alliance A031704) trial (NCT03793166) comprised 1111 patients across more than 500 academic centers in the United States, which was a major feat, Tan began. Thus far, the study’s primary end point has not been met, and the step 1 analysis continues to demonstrate patient outcomes after the first 3 months of induction with ipilimumab plus nivolumab, he explained. Although the inclusion and exclusion criteria were similar between the PDIGREE and phase 3 CheckMate 214 (NCT02231749) trials, Tan noted that the patient population in the PDIGREE trial was different. However, the PDIGREE study also included patients at community centers, which comprised more than 50% of the sites; therefore, there could have been a mix of patients with poorer prognoses and those with a baseline of higher burden of disease and poorer performance statuses, he continued.

Regarding safety, Tan explained that more grade 5 adverse effects were observed in the PDIGREE study compared with the CheckMate 214 study. Based on the results from the PDIGREE study, he emphasized that upfront IO regimens should be carefully considered. He reiterated that the goal of treatment is to produce durable complete responses, as seen in the CheckMate 214 study. Nevertheless, only focusing on IO treatment options could be a risky decision, particularly for patients who experience disease progression early, he asserted. Within 3 months of receiving ipilimumab plus nivolumab on the PDIGREE study, 35 patients had died on the study, he added. These patients likely had higher-risk disease with poorer clinical status and could have benefited from receiving IO/TKIs, including nivolumab plus cabozantinib (Cabometyx), pembrolizumab (Keytruda) plus axitinib (Inlyta), and lenvatinib (Lenvima) plus pembrolizumab, Tan concluded.