Abstract
The anti-PD1 antibody nivolumab is active and safe in metastatic clear-cell renal cell carcinoma.
Major finding: The anti–PD-1 antibody nivolumab is active and safe in metastatic clear-cell renal cell carcinoma.
Approach: Patients previously treated with antiangiogenic drugs were treated with nivolumab in a phase II trial.
Impact: Additional clinical trials of nivolumab treatment in metastatic renal cell carcinoma are warranted.
Interaction of programmed cell death 1 (PD-1) with its ligands PD-L1 and PD-L2 impairs antitumor T-cell responses and contributes to adaptive immune evasion and drug resistance, supporting the development of immunotherapies targeting these immune-checkpoint proteins. Treatment with nivolumab, a human antibody directed against PD-1, has been shown to induce objective responses in patients with various solid tumors, including metastatic renal cell carcinoma (RCC), in a phase I trial. Motzer and colleagues further evaluated the safety and efficacy of nivolumab in metastatic RCC and assessed whether a dose–response relationship exists in a randomized phase II trial. One hundred sixty-eight patients with metastatic clear-cell RCC who had experienced disease progression following treatment with antiangiogenic therapies, 70% of whom had received more than one prior systemic therapy, were randomly assigned to receive one of three doses of nivolumab. Importantly, no dose–response relationship for progression-free survival (PFS) was observed; median PFS ranged from 2.7 to 4.2 months and was increased when immune-related response criteria were applied. In addition, the objective response rate (ORR, 20% to 22%) and median overall survival (OS, 18.2 to 25.5 months) were similar across the three dose arms, and 14 out of 35 (40%) patients who achieved an objective response were ongoing responders at the end of the study. The incidence of treatment-related adverse events was similar across all doses, with fatigue being the most common event and grade 3 or 4 events occurring in 19 (11%) patients. Furthermore, assessment of tumor PD-L1 protein levels as an exploratory endpoint revealed that median PFS, ORR, and median OS were improved in patients with greater PD-L1 expression. These findings indicate that nivolumab shows antitumor activity with a manageable safety profile in patients with metastatic RCC and support ongoing phase III clinical trials of nivolumab.
Note: Research Watch is written by Cancer Discovery Science Writers. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org.
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