After a median follow-up of 45 months, the anti–PD-1 antibody nivolumab showed benefit in a majority of patients who had previously received one to five treatments for renal cell carcinoma, according to a report published online March 23 in the Journal of Clinical Oncology.

The previously treated cohort included 71% who had received two prior systemic treatments and 44% who had received three or more prior treatments for renal cell carcinoma (RCC). Out of the total 34 patients, 10 (29%) had objective responses, nine (27%) had stable disease for at least 24 weeks, 2 (6%) had stable disease for at least 48 weeks, and 3 patients (9%) had unconventional immune-related responses, which can include reduction in target lesions in the presence of new lesions or regression after initial progression (J. Clin. Oncol. 2015 Mar. 23 [doi:10.1200/JCO.2014.58.1041]).

“The results of our study suggest that nivolumab can be administered safely in an outpatient setting to pretreated patients with RCC and demonstrate durable clinical activity. Blockade of the PD-1 pathway may represent an important new target for RCC therapy,” wrote Dr. David F. McDermott of Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, and his colleagues. /

Adverse events of any grade were experienced by 29 (85%) patients, and 6 patients had grade 3-4 events. The toxicities, the most frequent of which were fatigue (14), rash (9), diarrhea (6), and pruritus (6), were consistent with immune-related mechanisms. The investigators noted that the favorable safety profile may permit the antibody to be used in combination and adjuvant regimens.

Patients received intravenous nivolumab 1 mg/kg (18 patients) or 10 mg/kg (16 patients) in an outpatient setting twice per week for up to 96 weeks. Some degree of tumor shrinkage occurred in 20 of 34 patients. Among the 10 patients with objective responses, the median duration was 12.9 months (range, 8.4-29.1+ months, with four responses ongoing at the time of analysis). Overall survival rates at 1, 2, and 3 years were 71%, 48%, and 44%, respectively, and the median overall survival was 22.4 months.

While the results are encouraging, the authors added that more research to understand the mechanism of action is needed to optimize the use of anti–PD-1 antibodies. Studies have shown that tumor expression of PD-L1 increases the likelihood of benefit from anti–PD-1, but not in all cases.

“A more comprehensive understanding of why some patients with PD-L1–negative tumors respond to PD-1 pathway blockade, while many with PD-L1–positive tumors fail to do so, will be critical to improving patient selection and developing anti–PD-1–based combination strategies for RCC,” they wrote.

Dr. McDermott reported having consulting or advisory roles with Bristol-Myers Squibb, Merck, Genentech/Roche, and Pfizer. Many of his coauthors reported ties to several industry sources.


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