Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma
Background Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have a poor prognosis and limited therapeutic options. First-line nivolumab plus ipilimumab (NIVO+IPI) provided efficacy benefits over sunitinib (SUN) in patients with intermediate/poor-risk sRCC at 42 months min...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/12/e005445.full |
| _version_ | 1797788528455712768 |
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| author | Chung-Wei Lee Thomas Powles Sabina Signoretti David F McDermott Sumanta K Pal Toni K Choueiri Brian I Rini Saby George Robert J Motzer Frede Donskov Scott S Tykodi Nizar M Tannir Saurabh Gupta Ruiyun Jiang |
| author_facet | Chung-Wei Lee Thomas Powles Sabina Signoretti David F McDermott Sumanta K Pal Toni K Choueiri Brian I Rini Saby George Robert J Motzer Frede Donskov Scott S Tykodi Nizar M Tannir Saurabh Gupta Ruiyun Jiang |
| author_sort | Chung-Wei Lee |
| collection | DOAJ |
| description | Background Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have a poor prognosis and limited therapeutic options. First-line nivolumab plus ipilimumab (NIVO+IPI) provided efficacy benefits over sunitinib (SUN) in patients with intermediate/poor-risk sRCC at 42 months minimum follow-up in the phase 3 CheckMate 214 trial. In this exploratory post hoc analysis, we report clinical efficacy of NIVO+IPI in sRCC after a minimum follow-up of 5 years.Methods In CheckMate 214, patients with clear cell advanced RCC were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks (four doses), then NIVO 3 mg/kg every 2 weeks versus SUN 50 mg once daily (4 weeks; 6-week cycles). Randomized patients with sRCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology report. Overall survival (OS), as well as progression-free survival (PFS) and objective response rate (ORR) per independent radiology review using Response Evaluation Criteria in Solid Tumors V.1.1, were evaluated in all International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor-risk sRCC patients and by baseline tumor PD-L1 expression level (≥1% vs <1%). Safety outcomes are reported using descriptive statistics.Results In total, 139 patients with intermediate/poor-risk sRCC were identified (NIVO+IPI, n=74; SUN, n=65). At 5 years minimum follow-up, more patients remained on treatment with NIVO+IPI versus SUN (12% vs zero). Efficacy benefits with NIVO+IPI versus SUN were maintained with median OS of 48.6 vs 14.2 months (HR 0.46), median PFS of 26.5 vs 5.5 months (HR 0.50), and ORR 60.8% vs 23.1%. In addition, median duration of response was longer (not reached vs 25.1 months), and more patients had complete responses (23.0% vs 6.2%) with NIVO+IPI versus SUN, respectively. Efficacy was better with NIVO+IPI versus SUN regardless of tumor PD-L1 expression, but the magnitude of OS, PFS, and ORR benefits with NIVO+IPI was greater for sRCC patients with tumor PD-L1 ≥1%. No new safety signals emerged in either arm with longer follow-up.Conclusions Among patients with intermediate/poor-risk sRCC, NIVO+IPI maintained long-term survival benefits and demonstrated durable and deep responses over SUN at minimum follow-up of 5 years, supporting NIVO+IPI as a preferred first-line therapy in this population.Trial registration number NCT02231749. |
| first_indexed | 2024-03-13T01:37:49Z |
| format | Article |
| id | doaj.art-635447aa98714bc2a7c7b60e0478a8aa |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-03-13T01:37:49Z |
| publishDate | 2022-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-635447aa98714bc2a7c7b60e0478a8aa2023-07-03T23:30:07ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-12-01101210.1136/jitc-2022-005445Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinomaChung-Wei Lee0Thomas Powles1Sabina Signoretti2David F McDermott3Sumanta K Pal4Toni K Choueiri5Brian I Rini6Saby George7Robert J Motzer8Frede Donskov9Scott S Tykodi10Nizar M Tannir11Saurabh Gupta12Ruiyun Jiang13Department of Clinical Trials, Bristol Myers Squibb, Princeton, New Jersey, USADepartment of Urology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London, UKDepartment of Pathology, Brigham and Women`s Hospital, Boston, Massachusetts, USADivision of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USADepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, USALank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Boston, MA, USADepartment of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USADepartment of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USADepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USADepartment of Oncology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Medicine, University of Washington and Fred Hutchinson Cancer Center, Seattle, Washington, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Translational Medicine, Bristol Myers Squibb, Princeton, New Jersey, USADivision of Biostatistics, Bristol Myers Squibb, Princeton, New Jersey, USABackground Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have a poor prognosis and limited therapeutic options. First-line nivolumab plus ipilimumab (NIVO+IPI) provided efficacy benefits over sunitinib (SUN) in patients with intermediate/poor-risk sRCC at 42 months minimum follow-up in the phase 3 CheckMate 214 trial. In this exploratory post hoc analysis, we report clinical efficacy of NIVO+IPI in sRCC after a minimum follow-up of 5 years.Methods In CheckMate 214, patients with clear cell advanced RCC were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks (four doses), then NIVO 3 mg/kg every 2 weeks versus SUN 50 mg once daily (4 weeks; 6-week cycles). Randomized patients with sRCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology report. Overall survival (OS), as well as progression-free survival (PFS) and objective response rate (ORR) per independent radiology review using Response Evaluation Criteria in Solid Tumors V.1.1, were evaluated in all International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor-risk sRCC patients and by baseline tumor PD-L1 expression level (≥1% vs <1%). Safety outcomes are reported using descriptive statistics.Results In total, 139 patients with intermediate/poor-risk sRCC were identified (NIVO+IPI, n=74; SUN, n=65). At 5 years minimum follow-up, more patients remained on treatment with NIVO+IPI versus SUN (12% vs zero). Efficacy benefits with NIVO+IPI versus SUN were maintained with median OS of 48.6 vs 14.2 months (HR 0.46), median PFS of 26.5 vs 5.5 months (HR 0.50), and ORR 60.8% vs 23.1%. In addition, median duration of response was longer (not reached vs 25.1 months), and more patients had complete responses (23.0% vs 6.2%) with NIVO+IPI versus SUN, respectively. Efficacy was better with NIVO+IPI versus SUN regardless of tumor PD-L1 expression, but the magnitude of OS, PFS, and ORR benefits with NIVO+IPI was greater for sRCC patients with tumor PD-L1 ≥1%. No new safety signals emerged in either arm with longer follow-up.Conclusions Among patients with intermediate/poor-risk sRCC, NIVO+IPI maintained long-term survival benefits and demonstrated durable and deep responses over SUN at minimum follow-up of 5 years, supporting NIVO+IPI as a preferred first-line therapy in this population.Trial registration number NCT02231749.https://jitc.bmj.com/content/10/12/e005445.full |
| spellingShingle | Chung-Wei Lee Thomas Powles Sabina Signoretti David F McDermott Sumanta K Pal Toni K Choueiri Brian I Rini Saby George Robert J Motzer Frede Donskov Scott S Tykodi Nizar M Tannir Saurabh Gupta Ruiyun Jiang Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma Journal for ImmunoTherapy of Cancer |
| title | Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma |
| title_full | Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma |
| title_fullStr | Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma |
| title_full_unstemmed | Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma |
| title_short | Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma |
| title_sort | long term outcomes with nivolumab plus ipilimumab versus sunitinib in first line treatment of patients with advanced sarcomatoid renal cell carcinoma |
| url | https://jitc.bmj.com/content/10/12/e005445.full |
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