University of Texas MD Anderson Cancer Center, Houston, TX
Jeremy Aaron Ross , Barrett Z. McCormick , Jianjun Gao , Pavlos Msaouel , Amado J. Zurita , Amishi Yogesh Shah , Eric Jonasch , Surena F. Matin , Christopher G. Wood , Jose A. Karam , Padmanee Sharma , Nizar M. Tannir , Matthew T. Campbell
Background: Pts with mRCC and sarcomatoid dedifferentiation (sRCC) have a poor prognosis with approved targeted therapies (Keskin et al. JU 2017). The response to ICIs in mRCC pts with sRCC is unknown. Methods: This is a retrospective study of pts with metastatic sRCC who received ICIs (2013-2017). Data collected include tumor histology, demographics, type of ICI, response to ICI, and efficacy outcomes (response, progression-free survival [PFS], and overall survival [OS]). Descriptive statistics were used. Results: 33 pts (85%) had clear-cell RCC (ccRCC); 6 pts had variant histology RCC (vhRCC) including chromophobe (2), mucinous tubular and spindle cell carcinoma (1), and unclassified (3). All pts but 2 had intermediate- or poor- risk disease by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. 15 pts (38%) had greater than 50% sarcomatoid component (sarc) in primary tumor of nephrectomy specimen, 5 (13%) had > 80%, and 2 (5%) had 100%. 22 pts (56%) received nivolumab (nivo) as a single agent. 15 pts (38%) received nivo in combination with ipilimumab and 2 pts (5%) received pembrolizumab. 24 pts (62%) responded to treatment with ICIs. Of these, 14 (58%) received ICIs at first-line therapy, 9 pts in second, 1 in fourth. Median PFS was 8.3 months (95% CI 3.6 – 13.1). 5/33 pts with ccRCC (15%) achieved a complete response (CR) and 4 remain in CR at 52, 31, 31, and 22 months from start of ICI. 1 pt was not followed at our institution after 24 months of CR. These pts had 90%, 1%, 30%, 50%, and 90% sarc, respectively. 1 of these patients remains on treatment. 5/6 pts with vhRCC did not respond to therapy; 1 pt with unclassified histology had stable disease for 5 months 28 pts (77%) are alive at time of this analysis. The median OS was not reached. Conclusions: In pts with sRCC, ICIs appear to be effective in ccRCC with up to 15% achieving durable CR. The prognosis of vhRCC with sRCC remains poor despite treatment with ICI, underscoring the need to develop more effective therapies for these patients.
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