Research Funding
GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Pharmaceutical/Biotech Company.
Background
NIVO showed an increased on OS in pre-treated mRCC. The introduction of metastasis SBRT could improve the clinical outcomes. NIVES Study evaluated the efficacy and safety of SBRT in combination with NIVO in II and III line of mRCC pts.
Methods
This is a phase II, single arm, multicentre study in mRCC pts with PD after ≤2 prior anti-angiogenic therapies with measurable metastatic sites, and at least one suitable for SBRT. The pts received hypofractionated radiation in 1 lesion at dose of 10 Gy/3 fractions after 7 days from the first infusion of NIVO. NIVO is given as flat dose of 240 mg on day 1 every 14 days for 6 months, then 480 mg q4-weekly in responding pts until PD or unacceptable toxicity. The primary end point is ORR. Secondary endpoints are PFS, OS, ORR of irradiated and non-irradiated metastasis and safety profile.
Results
69 pts were enrolled from July 2017 to March 2019 in 12 Italian centers. Pt characteristics were: 79.7% clear cell histology, 82.6% males, 79.7%% IMDC intermediate/poor, median age 67 yrs (43-85), 18.8% third line, 21.7% non-nephrectomy. The most frequent sites of SBRT were lung (37.7%), lymphonodes (15.9%), bone (11.6%). At the time of this analysis, median number of NIVO doses received was 12 (1-32). The ORR was 19% (1 CR) and DCR 63.5% (no statistically difference between site of SBRT and ORR); the largest benefit in pts with clear cell histology (p=0.01). Median PFS was 4 months (95%CI, 2.8-7.1), median OS 22.1 months (95%CI, 18.1-NR). With a median follow-up of 15 months (0-25.6), 6-month and 9-month survival rates were 80.3% and 56.1% respectively. 7 pts (10.1%) discontinued treatment due to AEs; grade(G) 3-4 toxicities related to NIVO were experienced in 17 pts (24.6%). The most frequent G3-4 toxicities included diarrhea (5.8%), amylase/lipase increased (4.3%) and hypothyroidism (4.3%); no G3-4 toxicities related to SBRT.
Conclusions
The NIVES Study represents the first prospective trial of NIVO and SBRT combination in pre-treated mRCC pts. At present the Study showed a high DCR and no-increase of toxicity. It is ongoing the analysis of correlation between efficacy and PD-L1 expression. Clinical trial information: NCT03469713