Cristina Masini1, Cinzia Iotti2, Ugo De Giorgi3, Roberto Salvatore Bellia4, Sebastiano Buti5, Francesco Salaroli6, Ilaria Zampiva7, Renzo Mazzarotto8, Claudia Mucciarini9, Maria Giuseppa Vitale10, Alessio Bruni11, Frank Lohr11, Giuseppe Procopio12, Orazio Caffo13, Franco Nole14, Franco Morelli15, Susanne Baier16, Consuelo Buttigliero17, Patrizia Ciammella2, Giorgia Timon2, Emanuela Fantinel18, Gabriele Carlinfante19, Annalisa Berselli18, Carmine Pinto18. 1. Medical Oncology Unit, Clinical Cancer Centre, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy. Electronic address: masini.cristina@ausl.re.it. 2. Radiation Oncology Unit, Clinical Cancer Centre, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy. 3. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 4. Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 5. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 6. Radiotherapy Unit, University Hospital of Parma, Parma, Italy. 7. Medical Oncology Unit, University Hospital, AOUI Verona, Italy. 8. Radiotherapy Unit, University Hospital, AOUI Verona, Italy. 9. Medical Oncology Unit, Ramazzini Hospital, Carpi, Italy. 10. Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy. 11. Radiation Therapy Unit, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy. 12. Department of Medical Oncology, Istituto Nazionale dei Tumori IRCCS, Milan, Italy. 13. Oncology Unit, S. Chiara Hospital, Trento, Italy. 14. Medical Oncology Division of Urogenital and Head & Neck Tumors IEO, European Institute of Oncology IRCCS, Milan, Italy. 15. Department of Oncology, IRCCS Ospedale Casa Sollievo della Sofferenza, Opera di Padre Pio, San Giovanni Rotondo, Italy. 16. Oncologia Medica Ospedale Regionale, Bolzano Azienda Sanitaria Alto Adige, Bolzano, Italy. 17. Department of Oncology, AOU San Luigi Gonzaga, University of Turin, Orbassano (Turin), Italy. 18. Medical Oncology Unit, Clinical Cancer Centre, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy. 19. Pathology Unit, Clinical Cancer Centre, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
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.
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.
Authors: Rohan R Katipally; Sean P Pitroda; Aditya Juloori; Steven J Chmura; Ralph R Weichselbaum Journal: Nat Rev Clin Oncol Date: 2022-07-12 Impact factor: 65.011
Authors: Jenny Bulgarelli; Claudia Piccinini; Elisabetta Petracci; Elena Pancisi; Anna Maria Granato; Francesco de Rosa; Massimo Guidoboni; Massimiliano Petrini; Valentina Ancarani; Giovanni Foschi; Antonino Romeo; Luca Tontini; Ugo De Giorgi; Cristian Lolli; Giorgia Gentili; Linda Valmorri; Alice Rossi; Fabio Ferroni; Carla Casadei; Pietro Cortesi; Laura Crudi; Laura Ridolfi Journal: Front Immunol Date: 2021-10-27 Impact factor: 7.561