Long-term follow-up of a phase I and a phase II study shows that nivolumab produces strong overall survival benefit in patients with advanced renal cell carcinoma (RCC). The analysis was presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held earlier this month in Chicago (abstract 4507).
The phase III CheckMate 025 study previously showed that nivolumab offers a survival benefit in previously treated advanced RCC over everolimus, which led to the drug’s approval in the United States and in Europe, said David F. McDermott, MD, of Beth Israel Deaconess Medical Center in Boston, who presented the new study. The follow-up in that survival analysis, though, only had a minimum of 14 months.
In the new analysis of the phase I and II studies, the authors focused on patients with a minimum follow-up of 48 months.
The phase I study had 34 patients, and the phase II study included 168 patients. Both had more male than female patients, and patients in the phase I study were more heavily pretreated.
Patients in the phase I trial had a median overall survival of 22.4 months; for the phase II study, the median overall survival was 23.4 months. About one-third of all patients were alive at 4 years, and 34% of the phase I patients were alive at 5 years from treatment initiation.
“We look forward to examining whether nivolumab produces similar long-term survival in the phase III trial,” McDermott said.
In those early studies, there was good survival in varying subgroups. Those with favorable MSKCC risk had a median overall survival of 35.5 months, compared with 22.1 months for intermediate-risk and 12.5 months for poor-risk patients. Patients who achieved a complete or partial response to nivolumab had not yet reached the median overall survival; those with stable disease had an overall survival of 22.9 months, and those with progressive disease as their best response had a median overall survival of 9 months. On the early analysis, CheckMate 025 also suggested benefit with nivolumab across risk groups.
Notably, there has not been significant emergence of long-term adverse events in the phase I and II patients. Grade 3/4 toxicity has occurred in 17.6% of phase I patients and 14.4% of phase II patients, and fewer than 10% in each study had treatment-related adverse events that led to discontinuation. McDermott noted that those adverse events outcomes are similar to those seen in CheckMate 025, even with 3 additional years of follow-up.
“Long-term survival is achievable regardless of risk group, performance status, or best overall response,” McDermott concluded. “Future investigations should focus on identification of predictors of long-term survival, determination of the optimal treatment duration of PD-1 blockade, and innovative trial designs to understand the clinical impact of sequential, adjuvant, and combination approaches.”
The discussant for the session, Daniel J. George, MD, of Duke Cancer Institute in Durham, North Carolina, noted that the relative lack of late treatment-related adverse events could indicate that some follow-up could be somewhat relaxed. Also, these results support the idea that the drug can change outcomes even in those without a good response to nivolumab.
“It would suggest that for patients, getting exposure to nivolumab, whether with a response or not, could be a good thing,” he said.