Background: Nivolumab showed an overall survival (OS) benefit in pretreated metastatic renal cell carcinoma (mRCC). The role of stereotactic body radiotherapy (SBRT) in mRCC remains to be defined. Objective: Our aim was to evaluate the efficacy and safety of SBRT in combination with nivolumab in second- and third-line mRCC patients. Design, setting, and participants: The NIVES study was a phase II, single-arm, multicenter trial in patients with mRCC with measurable metastatic sites who progressed after antiangiogenic therapy, of whom at least one was suitable for SBRT. Intervention: The patients received SBRT to a lesion at a dose of 10 Gy in three fractions for 7 d from the first infusion of nivolumab. Nivolumab was given at an initial dose of 240 mg every 14 d for 6 mo and then 480 mg q4-weekly in responding patients. Outcome measurements and statistical analysis: We hypothesized that nivolumab plus SBRT improves the objective response rate (ORR) compared with nivolumab alone from 25% (derived from historical controls) to 40%. Secondary endpoints were progression-free survival (PFS), OS, disease control rate (DCR) of irradiated and nonirradiated metastases, and safety. Results and limitations: Sixty-nine patients were enrolled from July 2017 to March 2019. The ORR was 17% and the DCR was 55%. The median PFS was 5.6 mo (95% confidence interval [CI], 2.9–7.1) and median OS 20 mo (95% CI, 17–not reached). After 1.5 yr of follow-up, 23 patients died. The median time to treatment response was 2.8 mo and median duration of response was 14 mo. No new safety concerns arose. Conclusions: We did not find sufficient evidence to suggest that nivolumab in combination with SBRT provides an added benefit in pretreated mRCC patients; it should however be evaluated in patients with oligometastatic or oligoprogressive disease. Patient summary: Nivolumab in combination with stereotactic body radiotherapy does not provide evidence of increased outcomes in metastatic renal cell carcinoma patients. However this approach was safe and showed a good response of the irradiated lesions.

Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES Study / Masini, C.; Iotti, C.; De Giorgi, U.; Bellia, R. S.; Buti, S.; Salaroli, F.; Zampiva, I.; Mazzarotto, R.; Mucciarini, C.; Vitale, M. G.; Bruni, A.; Lohr, F.; Procopio, G.; Caffo, O.; Nole, F.; Morelli, F.; Baier, S.; Buttigliero, C.; Ciammella, P.; Timon, G.; Fantinel, E.; Carlinfante, G.; Berselli, A.; Pinto, C.. - In: EUROPEAN UROLOGY. - ISSN 0302-2838. - (2022). [10.1016/j.eururo.2021.09.016]

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

Buti S.;Salaroli F.;
2022-01-01

Abstract

Background: Nivolumab showed an overall survival (OS) benefit in pretreated metastatic renal cell carcinoma (mRCC). The role of stereotactic body radiotherapy (SBRT) in mRCC remains to be defined. Objective: Our aim was to evaluate the efficacy and safety of SBRT in combination with nivolumab in second- and third-line mRCC patients. Design, setting, and participants: The NIVES study was a phase II, single-arm, multicenter trial in patients with mRCC with measurable metastatic sites who progressed after antiangiogenic therapy, of whom at least one was suitable for SBRT. Intervention: The patients received SBRT to a lesion at a dose of 10 Gy in three fractions for 7 d from the first infusion of nivolumab. Nivolumab was given at an initial dose of 240 mg every 14 d for 6 mo and then 480 mg q4-weekly in responding patients. Outcome measurements and statistical analysis: We hypothesized that nivolumab plus SBRT improves the objective response rate (ORR) compared with nivolumab alone from 25% (derived from historical controls) to 40%. Secondary endpoints were progression-free survival (PFS), OS, disease control rate (DCR) of irradiated and nonirradiated metastases, and safety. Results and limitations: Sixty-nine patients were enrolled from July 2017 to March 2019. The ORR was 17% and the DCR was 55%. The median PFS was 5.6 mo (95% confidence interval [CI], 2.9–7.1) and median OS 20 mo (95% CI, 17–not reached). After 1.5 yr of follow-up, 23 patients died. The median time to treatment response was 2.8 mo and median duration of response was 14 mo. No new safety concerns arose. Conclusions: We did not find sufficient evidence to suggest that nivolumab in combination with SBRT provides an added benefit in pretreated mRCC patients; it should however be evaluated in patients with oligometastatic or oligoprogressive disease. Patient summary: Nivolumab in combination with stereotactic body radiotherapy does not provide evidence of increased outcomes in metastatic renal cell carcinoma patients. However this approach was safe and showed a good response of the irradiated lesions.
2022
Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES Study / Masini, C.; Iotti, C.; De Giorgi, U.; Bellia, R. S.; Buti, S.; Salaroli, F.; Zampiva, I.; Mazzarotto, R.; Mucciarini, C.; Vitale, M. G.; Bruni, A.; Lohr, F.; Procopio, G.; Caffo, O.; Nole, F.; Morelli, F.; Baier, S.; Buttigliero, C.; Ciammella, P.; Timon, G.; Fantinel, E.; Carlinfante, G.; Berselli, A.; Pinto, C.. - In: EUROPEAN UROLOGY. - ISSN 0302-2838. - (2022). [10.1016/j.eururo.2021.09.016]
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