Abstract 737P
Background
After CARMENA and SURTIME, upfront cytoreductive nephrectomy (CN) is no longer standard of care. Intermediate and poor risk patients (pts) receive systemic therapy with the PT in place with the option to perform deferred CN in responding pts. This paradigm continues in the era of immune checkpoint inhibitor combination in frontline for mRCC. We assessed the safety and efficacy of this approach in a real-world setting.
Methods
A retrospective clinical audit of pts treated with first-line N+I and the PT in place at 3 institutions. Pts and tumour characteristics, International Metastatic RCC Database Consortium (IMDC) risk, overall response rate (ORR) in the PT and metastatic sites, time to response (TTR) of the PT, PT- and immune related- (ir) adverse events (AE), deferred CN rate, progression free- (PFS) and overall survival (OS) were analysed.
Results
Of 52 pts treated with N+I and the PT in place, 46.2% were IMDC poor risk and 44.2% had > 3 metastatic sites. After a median follow-up of 8 (2-12.5) months, 42 had at least 1 CT scan from baseline. Of those, 12 (23.1% [95% confidence interval [CI] 0.14-0.36]) had a partial response (PR) of the PT with a median TTR of 7.5 (3-12) months. Mean and median PT reduction were 18.9% (+16.7 to -73.9%) and 11.8 % from a baseline mean tumour size of 9 (2.5-16.1) cm. Pts with a PT reduction > median (n = 21) had a PR at metastatic sites in 80.9 % (CI 0.60-0.92) and progressive disease (PD) in only 1 case. Pts with PT reduction < median had PR in only 14.2 % and PD at metastatic sites in 57% (CI 0.37-0.76). None of the PT progressed. There was no complete response (CR) at metastatic sites. Only 2 CN were performed (3.8%) following PR at metastatic sites; 5 pts (9.6%) developed hematuria grade 1-3, requiring embolisation in 2 (3.8%). Grade 3-4 irAE were observed in 17% of pts. Median PFS and OS are 8.6 months and not reached.
Conclusions
N+I with the PT in place is safe and PT reduction is associated with response at metastatic sites. Most PT responded by 6-9 months. No CR at metastatic sites were observed (compared to a 9% CR rate in the pivotal trial) in this real-world population with a relatively high percentage of poor-risk pts. Furthermore, the deferred CN rate is low.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
E. Boleti: Research grant/Funding (institution): BMS. C.U. Blank: Honoraria (institution), Research grant/Funding (institution): BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer. J.B.A.G. Haanen: Honoraria (institution), Research grant/Funding (institution): BMS; Honoraria (institution): MSD; Honoraria (institution), Research grant/Funding (institution): Pfizer. T.B. Powles: Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Pfizer. A. Bex: Honoraria (institution), Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Ipsen; Honoraria (institution), Advisory/Consultancy: BMS; Advisory/Consultancy: Novartis. All other authors have declared no conflicts of interest.