Rechallenge of nivolumab in metastatic renal cell carcinoma, an ambispective multicenter study (RENIVO).

Abstract

330 Background: Immune checkpoint inhibitors (ICIs) in combination with another ICI or an antiangiogenic targeted therapy have been approved for frontline therapy in metastatic renal cell carcinoma (mRCC). However, progression disease (PD) often occurs and subsequent therapies are needed. Rechallenge of ICI may then be an option, but there is a lack of data regarding this strategy. Methods: This ambispective multicenter study included patients who received a rechallenge of Nivolumab (ICI-2) between January 2014 and September 2020, after a first-ICI therapy (ICI-1), regardless of the reason of the discontinuation. Patients could have either a non-ICI therapy or have a prolonged free-interval (≥ 12 weeks) between ICI regimens. Those with ongoing rechallenge at inclusion were followed prospectively. Primary endpoint was investigator-assessed best ORR. Results: 45 rechallenges were included from 16 centers. Median age was 60 years (range, 42-90), 64% were male. Most of them had clear cell histology (91%) and a Fuhrman or ISUP grade ≥ 3 (80%). Single-agent Nivolumab and Nivolumab-Ipilimumab association were used in 78% and 11% during ICI-1 and in 93% and 7% during ICI-2, respectively. Discontinuation for PD, toxicity or clinical decision occurred in 49%, 27% and 24% for ICI-1 and in 94%, 3% and 3% for ICI-2, respectively. The ORR were 51% (n = 23) at ICI-1 and 16% (n = 7) at ICI-2. One patient had a complete response during both ICI-1 and ICI-2 and two had a partial response at ICI-2 although they had PD as best ICI-1 response. After a median follow-up of 14.9 months (mo), median duration of response for ICI-2 was 5.1 mo (95% CI, 2.7-not reached [NR]). For ICI-1 and ICI-2: median progression-free survival (PFS) was 11.4 mo (95% CI, 9.8-23.5) and 3.5 mo (95% CI, 2.8-9.7); median overall survival was NR (95% CI, 37.8-NR) and 24 mo (95% CI, 9.9-NR). Poor prognostic factors for PFS at ICI-2 were Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2, presence of liver metastases, inflammatory syndrome and PFS under ICI-1 > 6 months. Grade ≥ 3 immune-related adverse events occurred in 24% (n = 11) during ICI-1 but only in 4% (n = 2) during ICI-2. There was no treatment-related death. Conclusions: Our study suggests that resumption of ICI with Nivolumab has a moderate efficacy in mRCC and acceptable tolerance. Predictive factors of response are needed to propose this strategy to selected mRCC patients. Larger prospective cohorts are needed to confirm these results. [Table: see text]