713P Treatment-free survival, with and without toxicity, after immuno-oncology vs targeted therapy for advanced renal cell carcinoma (aRCC): 42-month results of CheckMate 214

Regan, Meredith M.; Jegede, Opeyemi; Mantia, Charlene; Powles, Thomas; Werner, Lillian; Huo, Stephen; Tejo, Viviana Del; Stwalley, Brian; Atkins, Michael B.; McDermott, David F.

doi:10.1016/j.annonc.2020.08.785

Cited by 12 publications

(10 citation statements)

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“… 4 Additionally, a recent separate analysis suggests that while OS has appeared similar among FAV-risk patients between treatment arms, the way these patients experienced OS was notably different: SUN patients spent more time on protocol treatment with toxicity, whereas NIVO+IPI patients spent more time off treatment without toxicity. 12 …”

Section: Discussionmentioning

confidence: 99%

Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial

Albigès

Tannir

Burotto³

et al. 2020

ESMO Open

424

356

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PurposeTo report updated analyses of the phase III CheckMate 214 trial with extended minimum follow-up assessing long-term outcomes with first-line nivolumab plus ipilimumab (NIVO+IPI) versus (vs) sunitinib (SUN) in patients with advanced renal cell carcinoma (aRCC).MethodsPatients with aRCC with a clear cell component were stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk and randomised to NIVO (3 mg/kg) plus IPI (1 mg/kg) every three weeks ×4 doses, followed by NIVO (3 mg/kg) every two weeks; or SUN (50 mg) once per day ×4 weeks (6-week cycle). Efficacy endpoints included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) per independent radiology review committee in patients with intermediate/poor-risk disease (I/P; primary), intent-to-treat patients (ITT; secondary) and in patients with favourable-risk disease (FAV; exploratory).ResultsOverall, 1096 patients were randomised (ITT: NIVO+IPI, n=550, SUN, n=546; I/P: NIVO+IPI, n=425, SUN, n=422; FAV: NIVO+IPI, n=125, SUN, n=124). After 4 years minimum follow-up, OS (HR; 95% CI) remained superior with NIVO+IPI vs SUN in ITT (0.69; 0.59 to 0.81) and I/P patients (0.65; 0.54 to 0.78). Four-year PFS probabilities were 31.0% vs 17.3% (ITT) and 32.7% vs 12.3% (I/P), with NIVO+IPI vs SUN. ORR remained higher with NIVO+IPI vs SUN in ITT (39.1% vs 32.4%) and I/P (41.9% vs 26.8%) patients. In FAV patients, the HRs (95% CI) for OS and PFS were 0.93 (0.62 to 1.40) and 1.84 (1.29 to 2.62); ORR was lower with NIVO+IPI vs SUN. However, more patients in all risk groups achieved complete responses with NIVO+IPI: ITT (10.7% vs 2.6%), I/P (10.4% vs 1.4%) and FAV (12.0% vs 6.5%). Probability (95% CI) of response ≥4 years was higher with NIVO+IPI vs SUN (ITT, 59% (0.51 to 0.66) vs 30% (0.21 to 0.39); I/P, 59% (0.50 to 0.67) vs 24% (0.14 to 0.36); and FAV, 60% (0.41 to 0.75) vs 38% (0.22 to 0.54)) regardless of risk category. Safety remained favourable with NIVO+IPI vs SUN.ConclusionAfter long-term follow-up, NIVO+IPI continues to demonstrate durable efficacy benefits vs SUN, with manageable safety.Trial registration detailsClinicalTrials.gov identifier: NCT02231749.

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Section: Discussionmentioning

confidence: 99%

Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial

Albigès

Tannir

Burotto³

et al. 2020

ESMO Open

424

356

View full text Add to dashboard Cite

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“…In this trial, nearly 90% of 1096 intention-to-treat population had either intermediate or poor-risk disease, and in these patients, treatment with nivolumab plus ipilimumab resulted in superior 18-month OS. In favorable-risk patients, treatment with nivolumab plus ipilimumab resulted in inferior PFS and OS than sunitinib monotherapy, results which were confirmed at 42-month follow-up analysis [30]. As such, nivolumab plus ipilimumab is not indicated for first-line treatment in patients with favorable-risk disease at time of diagnosis.…”

Section: First Linementioning

confidence: 92%

“…ICI-specific outcome measures such as treatment free survival (TFS), defined as time from ICI cessation to subsequent systemic therapy initiation or death, should be considered in future clinical trials [38]. In favorable-risk patients in the CheckMate-214 trial, despite inferior outcomes to sunitinib monotherapy, patients treated with nivolumab plus ipilimumab achieved higher rates of complete response and duration of TFS [30]. These observations represent important patient-centered metrics that are critical to assess in future trials [39].…”

Section: First Linementioning

confidence: 99%

Immune Checkpoint Inhibitors for Genitourinary Cancers: Treatment Indications, Investigational Approaches and Biomarkers

Labadie

Balar

Luke

2021

Cancers

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Cancers of the genitourinary (GU) tract are common malignancies in both men and women and are a major source of morbidity and mortality. Immune checkpoint inhibitors (ICI) targeting CTLA-4, PD-1 or PD-L1 have provided clinical benefit, particularly in renal cell and urothelial carcinoma, and have been incorporated into standard of care treatment in both localized and metastatic settings. However, a large fraction of patients do not derive benefit. Identification of patient and tumor-derived factors which associate with response have led to insights into mechanisms of response and resistance to ICI. Herein, we review current approvals and clinical development of ICI in GU malignancies and discuss exploratory biomarkers which aid in personalized treatment selection.

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“…The overall survival benefits for the ITT population on nivolumab/ipilimumab relative to sunitinib in the Checkmate 214 study have remained stable over time with initial median follow-up of 25 months (HR OS = 0.68; P < 0.001) and interval follow-up at median 43 months (HR OS = 0.72; 0.61-0.86; P = 0.0002). Furthermore, Regan et al [64,65] analyzed 42-month TFS, defined as time from protocol therapy cessation to time of subsequent systemic therapy or death. In the nivolumab/ipilimumab arm, 56% of patients were alive, 13% were on nivolumab maintenance, and 31% were surviving free of subsequent therapy.…”

Section: Novel Endpointsmentioning

confidence: 99%

Current and emerging therapies for first line treatment of metastatic clear cell renal cell carcinoma

Serzan¹,

Atkins²

2021

JCMT

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The therapeutic landscape for advanced clear cell renal cell carcinoma (ccRCC) is rapidly evolving with improved knowledge of the biology of disease leading to the incorporation of a variety of antiangiogenic agents and immunotherapies. In this review, we discuss historical, current, and emerging first line treatment options for patients with advanced ccRCC. These include data with single agent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs): sunitinib, pazopanib and cabozantinib as well as the recently reported results for the combination of lenvatinib and everolimus (mTOR inhibitor). We also discuss results of the nivolumab anti-programmed cell death (PD-1)/ipilimumab (anti-cytotoxic T lymphocyte-associated antigen 4) combination as well as emerging front-line data with nivolumab and pembrolizumab (anti-PD-1) monotherapy. Finally, we review data supporting recent approvals of TKI and anti-PD-1 or anti-PD-Ligand 1 (PD-L1) combinations (e.g., axitinib/pembrolizumab, axitinib/avelumab and cabozantinib/nivolumab) and initial outcomes of lenvatinib (multi-kinase inhibitor) and pembrolizumab. With many individual and combination treatment options and the lack of head-to-head comparisons, treatment selection will depend on the goals of therapy (endpoints) and the identification and validation of clinical and tumor-based predictive biomarkers that are linked to the desired treatment endpoints.

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713P Treatment-free survival, with and without toxicity, after immuno-oncology vs targeted therapy for advanced renal cell carcinoma (aRCC): 42-month results of CheckMate 214

Abstract: Treatment-free survival, with and without toxicity, after immunooncology vs targeted therapy for advanced renal cell carcinoma (aRCC): 42-month results of CheckMate 214

Cited by 12 publications

References 0 publications

Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial

Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial

Immune Checkpoint Inhibitors for Genitourinary Cancers: Treatment Indications, Investigational Approaches and Biomarkers

Current and emerging therapies for first line treatment of metastatic clear cell renal cell carcinoma

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