Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES Study

Masini, Cristina; Iotti, Cinzia; Giorgi, Ugo De; Bellia, Roberto Salvatore; Buti, Sebastiano; Salaroli, F.; Zampiva, Ilaria; Mazzarotto, Renzo; Mucciarini, Claudia; Vitale, Maria Giuseppa; Bruni, Alessio; Lohr, Frank; Procopio, Giuseppe; Caffo, Orazio; Nolè, Franco; Morelli, Franco; Baier, Susanne; Buttigliero, Consuelo; Ciammella, Patrizia; Timon, G.; Fantinel, Emanuela; Carlinfante, Gabriele; Berselli, Annalisa; Pinto, Carmine

doi:10.1016/j.eururo.2021.09.016

Cited by 63 publications

(41 citation statements)

References 28 publications

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“…The 2-year PFS and local control were 45% and 92%, respectively. The NIVES study 107 evaluated the addition of SABR with nivolumab; 26% experienced grade 3-4 treatment-related AEs and 7% discontinued therapy. In a meta-analysis 108 of radiotherapy and ICIs, there were similar grade 3-4 toxicities in ICIs plus radiotherapy (17.8%; 95% CI, 12.0 to 24.5) compared with ICIs alone (22.4%; 95% CI, 18.4 to 26.6).…”

Section: Recommendationsmentioning

confidence: 99%

Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline

Rathmell

Rumble

Veldhuizen

et al. 2022

JCO

143

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PURPOSE To provide recommendations for the management of patients with metastatic clear cell renal cell carcinoma (ccRCC). METHODS An Expert Panel conducted a systematic literature review to obtain evidence to guide treatment recommendations. RESULTS The panel considered peer-reviewed reports published in English. RECOMMENDATIONS The diagnosis of metastatic ccRCC should be made using tissue biopsy of the primary tumor or a metastatic site with the inclusion of markers and/or stains to support the diagnosis. The International Metastatic RCC Database Consortium risk criteria should be used to inform treatment. Cytoreductive nephrectomy may be offered to select patients with kidney-in-place and favorable- or intermediate-risk disease. For those who have already had a nephrectomy, an initial period of active surveillance may be offered if they are asymptomatic with a low burden of disease. Patients with favorable-risk disease who need systemic therapy may be offered an immune checkpoint inhibitor (ICI) in combination with a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI); patients with intermediate or poor risk should be offered a doublet regimen (no recommendation was provided between ICIs or an ICI in combination with a VEGFR TKI). For select patients, monotherapy with either an ICI or a VEGFR TKI may be offered on the basis of comorbidities. Interleukin-2 remains an option, although selection criteria could not be identified. Recommendations are also provided for second- and subsequent-line therapy as well as the treatment of bone metastases, brain metastases, or the presence of sarcomatoid features. Participation in clinical trials is highly encouraged for patients with metastatic ccRCC. Additional information is available at www.asco.org/genitourinary-cancer-guidelines

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Section: Recommendationsmentioning

confidence: 99%

Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline

Rathmell

Rumble

Veldhuizen

et al. 2022

JCO

143

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“…In the combination of radiotherapy and nivolumab, a phase 2 trial, the NIVES trial, showed that an ORR of irradiated lesions (29%) was higher than that of nonirradiated metastases (12%) and disease control rate of irradiated lesions (85%). However, the ORR was 17%, the median PFS was 5.6 months (95% CI 2.9–7.1), and the median OS was 20 months (95% CI 17–not reached), which did not provide sufficient evidence to increase benefits with radiotherapy 64 . The NIVOIGERCC trial (jRCTs031180024) is a prospective randomized trial comparing image guided SBRT with nivolumab and nivolumab alone.…”

Section: Metastasectomy and Focal Treatment For Metastatic Lesionsmentioning

confidence: 99%

“…However, the ORR was 17%, the median PFS was 5.6 months (95% CI 2.9-7.1), and the median OS was 20 months (95% CI 17-not reached), which did not provide sufficient evidence to increase benefits with radiotherapy. 64 The NIVOIGERCC trial (jRCTs031180024) is a prospective randomized trial comparing image guided SBRT with nivolumab and nivolumab alone. The primary endpoint is ORR of nonirradiated lesions at the end of 12 cycle-nivolumab, which could estimate "abscopal effect.…”

Section: Metastasectomy and Focal Treatment For Metastatic Lesionsmentioning

confidence: 99%

Surgical and focal treatment for metastatic renal cell carcinoma: A literature review

2022

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Abbreviations & Acronyms AS = active surveillance cCa = corrected calcium CI = confidence interval CN = cytoreductive nephrectomy CNS = central nervous system CR = complete response HR = hazard ratio ICI = immune checkpoint inhibitor IFN-a = interferon alpha IMDC = International Metastatic RCC Database Consortium IPTW = propensity scorebased inverse probability of treatment weight KPS = Karnofsky performance status mRCC = metastatic renal cell carcinoma NLR = neutrophil-tolymphocyte ratio ORR = objective response rate OS = overall survival PFS = progression-free survival RCC = renal cell carcinoma RCT = randomized controlled trial REMARCC = registry for metastatic renal cell carcinoma SBRT = stereotactic radiation therapy SRS = stereotactic radiosurgery TT = targeted therapy WBRT = whole-brain radiotherapy

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“…Our study might share some similarities with the NIVES study, in which the investigators did not meet the primary end point of improving response rate to 40% even if it showed an important DCR and low toxicity ( 49 ). Similar to our study, the NIVES study has some limitations e.g.…”

Section: Discussionmentioning

confidence: 78%

Radiotherapy and High-Dose Interleukin-2: Clinical and Immunological Results of a Proof of Principle Study in Metastatic Melanoma and Renal Cell Carcinoma

et al. 2021

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High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed. We designed a phase II, single-arm clinical trial for patients with MM and RCC. The treatment schedule consisted of 3 daily doses of 6-12 Gy of RT to 1-5 non-index metastatic fields, before IL-2 at the first and third treatment cycle. HD IL-2 was administered by continuous infusion for 72 hours and repeated every 3 weeks for up to 4 cycles, thereafter every 4 weeks for a maximum of 2 cycles. The primary endpoint was the immunological efficacy of the combined RT/HD IL-2 treatment (assessed by IFN-γ ELISPOT). Nineteen out of 22 patients were evaluable for immunological and clinical response. Partial response occurred in 3 (15.7%) patients and stable disease was observed in 7 (36.8%). The disease control rate was 52.6% after a median follow up of 39.2 months. According to Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0), the majority of toxicities were grade 1-2. Immunological responses were frequent and detected in 16 (84.2%) patients. Increased levels of IL-8 and IL-10 in melanoma, circulating effector memory CD4+ and intratumoral CD8+ T cells in both tumor types were detected after therapy. Overall the treatment was well tolerated and immunologically active. Immunomonitoring and correlative data on tumor and peripheral blood cell subsets suggest that this combination treatment could be a promising strategy for patients progressing after standard treatments.

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Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES Study

Cited by 63 publications

References 28 publications

Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline

Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline

Surgical and focal treatment for metastatic renal cell carcinoma: A literature review

Radiotherapy and High-Dose Interleukin-2: Clinical and Immunological Results of a Proof of Principle Study in Metastatic Melanoma and Renal Cell Carcinoma

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