Treatment sequence after first-line nivolumab plus ipilimumab or sunitinib monotherapy in patients with metastatic renal cell carcinoma (mRCC) using real-world data.

Abstract

288 Background: The introduction of second-line (2L) nivolumab (NIVO) in 2015 (CheckMate 025) and first-line (1L) NIVO plus ipilimumab (NIVO+IPI) in 2018 (CheckMate 214) revolutionized the management of mRCC in the US. This study sought to leverage real-world (RW) data by applying CheckMate 214 inclusion criteria to develop a RW comparator for the trial to assess treatment patterns and sequences in RW patients (pts) with mRCC after receiving 1L NIVO+IPI or sunitinib (SUN). Methods: This retrospective study identified pts with clear cell mRCC from the Flatiron Health EHR-derived de-identified database who received 1L NIVO+IPI or SUN monotherapy on or after December 2015. Pts must have met the strict selection criteria from CheckMate 214 for this analysis. Evaluation of 1L, 2L, and third-line (3L) therapies was stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk (favorable [FAV] and intermediate/poor [I/P]). Results: Of 401 mRCC pts included in the study, 197 (49.1%) received NIVO+IPI and 204 (50.9%) received SUN as 1L therapy (Table). The median follow-up time was 10.1 months in NIVO+IPI pts and 20.2 months in SUN pts ( P < 0.0001). Among 66 (33.5%) NIVO+IPI pts who received 2L line therapy, the 2 most common therapies were cabozantinib (CABO; 50.0%), and pazopanib (PAZO; 12.1%). Among 119 (58.3%) SUN pts who received 2L therapy, the most common therapies were NIVO (48.7%), and PAZO (8.4%). The 2 most common 3L therapies were axitinib (AXI; 18.2%) or everolimus plus lenvatinib (EVE+LEN; 18.2%) for NIVO+IPI pts, and CABO (26.7%) or NIVO (15.0%) for SUN pts. The treatment sequence is similar between patients with FAV and I/P risk. Conclusions: In the RW setting, the treatment sequences after NIVO+IPI and SUN were largely similar across the IMDC risk groups. CABO was the most common therapy in 2L after NIVO+IPI in RW pts, and NIVO was the most common 2L therapy after SUN monotherapy, which was consistent with the sequence in the trial. [Table: see text]

Real-world Treatment Patterns and Clinical Outcomes for Metastatic Renal Cell Carcinoma in the Current Treatment Era

“…Consistent with the study by Zakharia et al [17] , we observed a marked increase in the uptake of both pembrolizumab + axitinib and ipilimumab + nivolumab combinations since their respective FDA approval. In our study, consistent with the literature [18] , [19] , [20] , [21] , 2L therapies were guided by 1L therapies: patients received TKI monotherapy after IO-based 1L treatment, and received an IO-based therapy after TKI-based 1L treatment. Cabozantinib was the most common 2L therapy among patients receiving IO-based 1L therapy, and nivolumab was the most common 2L therapy among patients receiving 1L TKI monotherapy.…”

Real world treatment sequences and outcomes for metastatic renal cell carcinoma

“…We observed a trend toward an increasing use of ipilimumab plus nivolumab and pembrolizumab plus axitinib after the FDA approval. Literatures reported that second-line therapies are affected by the first-line treatments:patients received TKIs after IO-based therapies; patients received IO-based therapiesafterTKIs treatment [11,13,14]. The present study also observed a similar finding: for patients receiving ipilimumab plus nivolumabor pembrolizumab plus axitinib as first-line therapy, the most common second-line treatment was cabozantinib (54.6%).…”

“…Several phase III clinical trials demonstrated the efficacy of such combination therapies, including CheckMate 214 (Ipilimumab + Nivolumab versus Sunitinib), KEYNOTE-426 (axitinib + pembrolizumab versus sunitinib),CHECKMATE-9ER (cabozantinib + nivolumab versus sunitinib), CLEAR (pembrolizumab + lenvatinib versus sunitinib), and JAVELINtrial (avelumab + axitinib versus sunitinib) [2][3][4][5][6][7]. However, only a few studies reported real-world data regarding treatment pattern and clinical outcome of combination therapies on RCC [11][12][13][14]. In this era of IO and TKI targeted therapy, it is important to understand the treatment efficacy and sequence of these agents.…”