Nivolumab Rechallenge Associated with Moderate Efficacy

2021 Year in Review - Renal-Cell Carcinoma

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


  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.

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