Abstract 728P
Background
ICI have revolutionized first-line treatment paradigm of mRCC, achieving durable responses and longer survival. However, a subset of patients (pts) developed resistance immediately (PrR) or after an initial clinical benefit (AcR). The aim of the study is to identify key differences between these two subgroups.
Methods
Retrospective analysis was performed from IGReCC (Institut Gustave Roussy Renal Cell Carcinoma) database on pts treated with first line ICI. PrR was defined as progression disease (PD) or stable disease (SD) lasting <6 months (mo) as best response; AcR was defined as complete, partial or SD≥6 mo. Statistical tests as appropriate were used to describe differences between groups and investigated established prognostic markers (IMDC, metastatic sites). The Kaplan-Meier and Cox regression methods were used to estimate overall survival (OS).
Results
A total of 50 pts received first-line treatment with ICI and were evaluated for best response. The majority of pts (86%) received Nivo+Ipi and 8 pts (6%) received ICI monotherapy (6 nivo, 2 atezo). PrR and AcR were 21 (42%) and 29 (58%) respectively. PrR and AcR groups were compared for main clinical features and only significant differences are reported in the table and considered for multiple regression. From multivariate analysis time to treatment start (TTT) (odds ratio [OR] 19.4; 95%CI 1.7-224, p=0.016) and number of metastatic sites ≥3 (OR 10.2; 95%CI 1.8-56.1, p=0.005) seems associated with PrR. With a median follow-up of 19 mo (range 1-55), 12mo-OS rate was 96% (95%CI 72-99) vs 53% (95%CI 25-75) and 24mo-OS rate was 81% (95%CI 48-94) vs 35% (95%CI 12-62) for AcR and PrR, respectively HR 5.8 (95%CI 1.8-18.9), p 0.0009. Table: 728P
| PrR N/% | AcR N/% | p | |
| TTT ≤1 year | 20/95 | 19/66 | 0.016 |
| Metastatic sites ≥3 | 12/60 | 4/17 | 0.005 |
| Haemoglobin < LNL | 11/52 | 7/25 | 0.049 |
Conclusions
Deciphering first-line PrR and AcR subsets of pts may become a key challenge for decision-making in mRCC. This is the first report to describe different patterns of resistance potentially related to different clinical outcomes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Has not received any funding.
Disclosure
B. Escudier: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Oncogena; Advisory/Consultancy, Travel/Accommodation/Expenses: AVEO; Advisory/Consultancy: EUSA. L. Albiges: Honoraria (institution): Novartis; Honoraria (institution): Amgen; Honoraria (institution): BMS; Honoraria (institution): Ipsen; Honoraria (institution): Roche; Honoraria (institution): Pfizer; Honoraria (institution): Astellas; Honoraria (institution): Merck; Honoraria (institution): AstraZeneca; Honoraria (institution): Exelis; Honoraria (institution): MSD; Honoraria (institution): Corvus Pharmaceuticals; Honoraria (institution): Peloton terapeutics. All other authors have declared no conflicts of interest.