Nivolumab in Renal-Cell Carcinoma

Posted by • November 6th, 2015

Kaplan-Meier CurveIn a randomized trial involving patients with advanced previously treated renal-cell carcinoma, nivolumab produced higher response rates than everolimus (25% vs. 5%) and median overall survival was longer (by 5.4 months), to more than 2 years. A new Original Article summarizes.

Each year, an estimated 338,000 new cases of renal-cell carcinoma are diagnosed worldwide, and approximately 30% of patients present with metastatic disease at the time of diagnosis. A number of targeted therapies have been approved for the treatment of advanced or metastatic renal-cell carcinoma. Although everolimus and other agents  have changed the therapeutic landscape for this disease, these treatments are associated with limited overall survival after a given agent is no longer effective. Motzer et al. conducted a randomized, open-label, phase 3 study that compared nivolumab with everolimus in patients with advanced renal-cell carcinoma, who had previously received one or two cycles of antiangiogenic therapy.

Clinical Pearls

• Does nivolumab as compared to everolimus prolong survival in patients with renal-cell carcinoma who have previously received one or two cycles of antiangiogenic therapy?

In the study by Motzer et al., patients with advanced renal-cell carcinoma who had received previous antiangiogenic treatment had longer survival with nivolumab treatment than with everolimus treatment. The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) in the nivolumab group and 19.6 months (95% CI, 17.6 to 23.1) in the everolimus group. Death occurred in 183 of the 410 patients (45%) randomly assigned to receive nivolumab and in 215 of the 411 patients (52%) randomly assigned to receive everolimus. The hazard ratio for death (from any cause) with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority.

Figure 1. Kaplan-Meier Curve for Overall Survival.

• Is nivolumab associated with a higher objective response rate than everolimus in previously treated patients?

In the study by Motzer et al., the objective response rate was higher with nivolumab than with everolimus (25% vs. 5%; odds ratio 5.98; 95% CI, 3.68 to 9.72; P<0.001). Partial responses were observed in 99 patients (24%) in the nivolumab group and in 20 patients (5%) in the everolimus group. Complete responses were observed in 4 patients (1%) in the nivolumab group and in 2 patients (<1%) in the everolimus group.

Morning Report Questions

Q: Is nivolumab associated with fewer treatment-related adverse events as compared to everolimus?

A: In the Motzer trial, treatment-related adverse events of any grade occurred in 319 of the 406 patients (79%) treated with nivolumab and in 349 of the 397 patients (88%) treated with everolimus. Grade 3 or 4 treatment-related adverse events occurred in 76 of the 406 patients (19%) treated with nivolumab and in 145 of the 397 patients (37%) treated with everolimus; the most common grade 3 or grade 4 event was fatigue (10 patients, 2%) with nivolumab and anemia (31 patients, 8%) with everolimus.

Table 2. Treatment-Related Adverse Events Reported in 10% or More of Treated Patients in Either Group.

Q: Was the benefit observed with nivolumab in the Motzer study linked to programmed death 1 ligand (PD-L1) expression in tumors?

A: A benefit was observed with nivolumab irrespective of PD-L1 expression. Nivolumab has been reported to be associated with pharmacodynamic changes in blood and tumor markers that are consistent with PD-1 inhibition. The study data corroborate previous studies that have indicated that higher levels of PD-L1 expression are associated with poorer survival in renal-cell carcinoma, but they do not support PD-L1 as a marker of treatment benefit in renal-cell carcinoma. The relationship between PD-L1 expression and outcomes after treatment with nivolumab appears to depend on tumor type and histologic class. An association between PD-L1 expression and improved outcomes with nivolumab treatment has been observed for metastatic melanoma and only some types of lung cancer.

Figure 3. Kaplan-Meier Curve for Overall Survival, According to Programmed Death 1 Ligand (PD-L1) Expression Level.

One Response to “Nivolumab in Renal-Cell Carcinoma”

  1. Eddyniu says:

    How about the quality of life? If patients get life for 6 more months but poor quality, i don’t think that it’s a good news.