Nivolumab Rechallenge Associated with Moderate Efficacy

Nivolumab is an immune checkpoint inhibitor (ICI) that is approved for use in a variety of renal-cell carcinoma (RCC) settings.^1,2 Nivolumab plus ipilimumab is approved for use in patients with intermediate- or poor-risk, untreated, advanced RCC. Nivolumab plus cabozantinib is approved as a first-line option for patients with advanced RCC. Finally, nivolumab monotherapy is an option for patients who have received previous antiangiogenic therapy.² However, limited data are available for the use of nivolumab in patients who have been previously treated with an ICI.¹

In this multicenter study, 45 patients who received nivolumab rechallenge after first-line ICI between January 2014 and September 2020 were included. Patients who were still receiving nivolumab at the time of study inclusion were followed prospectively. Investigator-assessed best overall response rate was the primary end point.¹

Most enrolled patients had clear-cell RCC (91%) and Fuhrman grade of ≥3 (80%). First-line ICI use was primary nivolumab (78%) followed by nivolumab plus ipilimumab (11%). In the rechallenge setting, nivolumab was used as a monotherapy in 93% of cases and in combination with ipilimumab in 7% of cases. In the first-line ICI and second-line ICI settings, discontinuations were attributed to progressive disease (49% and 94%, respectively), toxicity (27% and 3%, respectively), or clinical decision (24% and 3%, respectively).¹

Overall response rate with the first ICI was 51% and dropped to 16% for the second ICI. A single patient achieved a complete response in the first-line and second-line ICI settings. Two patients who had progressive disease as best response to ICI in the first-line setting had partial responses with nivolumab rechallenge.¹

Patients were followed for a median of 14.9 months, during which the median duration of response to nivolumab rechallenge was 5.1 months (95% confidence interval [CI], 2.7-not reached [NR]). Median progression-free survival was 11.4 months with the first ICI (95% CI, 9.8-23.5) and 3.5 months with the second ICI (95% CI, 2.8-9.7). Median overall survival was NR with the first ICI (95% CI, 37.8-NR) and 24 months with the second ICI (95% CI, 9.9-NR). Progression-free survival with the second ICI was negatively affected by Eastern Cooperative Oncology Group performance status ≥2, liver metastases at inclusion, presence of inflammatory syndrome, and progression-free survival with the first ICI of >6 months.¹

Immune-related adverse events of grade ≥3 were reported in 24% of patients with the first ICI and in 4% of patients with the second ICI. No treatment-related deaths were reported.¹

The investigators concluded that nivolumab rechallenge is moderately effective and safe; however, predictive biomarkers are needed to identify candidate patients.¹

References

1. Vauchier C, Auclin E, Barthelemy P, et al. J Clin Oncol. 2021;39(6_suppl):Abstract 330.
2. Opdivo (nivolumab) injection, for intravenous use [prescribing information]. Bristol Myers Squibb; September 2021.