Nivolumab (NIVO) in combination with stereotactic body radiotherapy (SBRT) in pretreated patients (pts) with metastatic renal cell carcinoma (mRCC): First results of phase II NIVES study.

Abstract

613 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.

Radiation and Checkpoint Inhibitor Immunotherapy Lead to Long Term Disease Control in a Metastatic RCC patient With Brain Metastases

“…Progression-free survival was 4.1 months, median OS was 22.07 months, and 1-year PFS and OS rates were 32.6 and 73.4%, respectively. Grade 3-4 toxicities were observed in 24.6% of patients and none of these occurred within the radiation field (31). RADVAX RCC evaluated the combination of nivolumab and ipilimumab with SBRT, with most patients having previously undergone nephrectomy (68%).…”

Adrenal Metastases as Sanctuary Sites in Advanced Renal Cancer

“…Systemic therapy with vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) should be considered to achieve tumor size reduction and then attempt local therapy to render complete remission. The recent results of combinations of stereotactic body radiation therapy (SBRT) and immune checkpoint-based systemic therapy studies have demonstrated response rates and overall outcomes no different than those with systemic therapy alone ( 8 , 9 ). However, if adrenal lesions are present as a sanctuary site after immune therapy, then use of local therapy is indicated.…”

Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments

“…The NIVES study, a phase II multicenter trial evaluated the combination of nivolumab (240 mg every 2 weeks) with SBRT (10 Gy × 3 fractions 7 days after the first infusion of nivolumab) in advanced RCC that progressed on up to two prior systemic therapies [41]. The primary endpoint was not reached with an objective response rate of 17.4% (for an expected rate of 40%).…”