Nivolumab (N) is a standard of care in patients (pts) with metastatic RCC after failure of 1 or 2 TKIs. Efficacy of N on brain metastases (BM) from RCC is still unknown.
GETUG-AFU 26 (NIVOREN) is a prospective phase 2 trial assessing safety and efficacy of N in real-world mRCC pts population. This trial included pts with BM not requiring steroids. Herein, we report BM response to N and clinical outcomes in this subpopulation.
Overall, 81/709 (11%) pts had active BM or history of BM. Among them, 72 with visible BM at baseline and treated with N were included for analysis. IMDC risk groups were: favorable in 13 pts (18%), intermediate in 34 (48%), poor in 24 (34%). N was given in 2nd or 3rd line in 74% of pts. Median follow up was 16.1 months (m). Among 72 pts, 33 (46%) had no prior local therapy for BM, and 39 (54%) had prior local therapy: 29 had radiation therapy (RT) including 25 pts with stereotactic and 4 with whole brain RT, and 10 had prior surgery plus RT. Number of BM at baseline was 1 in 45 pts (62.5%), 2 or 3 in 17 (23.6%), >3 in 10 (13.9%). Median PFS was 2.8m [CI95% 2.5-4.2], 12m-OS was 61.7% [CI95% 48.5-72.5]. Response assessment on BM was available in 64 pts, among which 11 (17.2%) had objective response (Table 1). Under N, neurologic deterioration was observed in 29 pts (41%) and 28 (39%) required steroids. Overall, 35/72 (49%) pts required focal treatment: 27/33 (82%) in untreated pts and 8/39 (20.5%) in previously treated pts. 6m-brain PFS was 24.5% in untreated pts vs 44.8% in previously treated pts. Correlation between systemic RECIST and brain RECIST will be reported.Table: 868PD Brain objective response (modified RECIST).
|Untreated (N = 33)||Prior focal treatment (N = 39)||Overall (N = 72)|
|CR||4* (13.3%)||3 (8.8%)||7 (10.9%)|
|PR||0 (0.0%)||4 (11.8%)||4 (6.3%)|
|SD||12 (40.0%)||16 (47.1%)||28 (43.8%)|
|PD||14 (46.7%)||11 (32.4%)||25 (39.1%)|
2/4 pts developed new BM on subsequent brain imaging**
not assessed due to early clinical progression.
This is the first study to report activity of N in pts with and without prior focal treatment of BM from RCC. In pts without prior BM focal therapy, N efficacy was poor, and most pts required local treatment for brain progression.
Clinical trial identification
Legal entity responsible for the study
R. Flippot: Travel grants: Pfizer, Novartis B. Laguerre: Honoraria: Bristol-Myers Squibb, Bristol-Myers Squibb, Novartis, Pfizer, Sanofi; Travel, accommodations, expenses: Bristol-Myers Squibb, Bristol-Myers Squibb, Janssen Oncology, Novartis; Pfizer. D. Borchiellini, C.M. Chevreau: Consulting or advisory role: Bristol-Myers Squibb, Ipsen, Novartis, Pfizer, G. Gravis: Travel, accommodations, expenses: Astellas Pharma, Bristol-Myers Squibb, Janssen, Oncology, Novartis, Sanofi, Takeda. S. Negrier: Honoraria: Bristol-Myers Squibb, EUSA Pharma, Ipsen, Novartis, Pfizer Consulting; Advisory role: Bristol-Myers Squibb, EUSA Pharma; Research funding: Novartis (Inst), Pfizer (Inst); Travel, accommodations, expenses: Bristol-Myers Squibb, Pfizer. F. Joly: Consulting or advisory role: AstraZeneca, BMS Brazil, Janssen, Novartis, Roche, Sanofi, Tesaro; Research funding: Astellas Pharma, Janssen; Travel, accommodations, expenses: AstraZeneca, Janssen, Roche, Tesaro. B. Escudier: Honoraria: Bayer, Bristol-Myers Squibb, Exelixis, Ipsen, Novartis, Pfizer, Roche/Genentech; Consulting or advisory role: Bayer, Bristol-Myers Squibb, EUSA Pharma, Exelixis, Ipsen, Novartis, Pfizer; Travel, accommodations, expenses: Bristol-Myers Squibb, Novartis, Pfizer. L. Albiges: Consulting or advisory role: Amgen, Bayer, Bristol-Myers Squibb, Bristol-Myers Squibb (Inst), Ipsen (Inst), Novartis, Pfizer, Sanofi; Research funding: (Inst): Bristol-Myers Squibb, Novartis, Pfizer. All other authors have declared no conflicts of interest.