Presentation on theme: "CheckMate 025: A randomized, open-label, phase III study of nivolumab versus everolimus in advanced renal cell carcinoma Padmanee Sharma, Bernard Escudier,"— Presentation transcript:
1 CheckMate 025: A randomized, open-label, phase III study of nivolumab versus everolimus in advanced renal cell carcinomaPadmanee Sharma, Bernard Escudier, David F. McDermott, Saby George, Hans J. Hammers, Sandhya Srinivas, Scott S. Tykodi, Jeffrey A. Sosman, Giuseppe Procopio, Elizabeth R. Plimack, Daniel Castellano, Howard Gurney, Frede Donskov, Petri Bono, John Wagstaff, Thomas C. Gauler, Takeshi Ueda, Li-An Xu, Ian M. Waxman, Robert J. Motzer, on behalf of the CheckMate 025 investigators
2 IntroductionEach year, an estimated 338,000 new cases of renal-cell carcinoma are diagnosed worldwide, and approximately 30% of patients present with metastatic disease at the time of diagnosisA number of targeted therapies have been approved for the treatment of advanced or metastatic RCC based on PFSCurrent therapies provide limited OS benefit in patients who have been previously treated, highlighting a significant unmet medical needThis phase III study compared nivolumab, a PD-1 immune checkpoint inhibitor, versus everolimus in patients with mRCC after prior systemic therapyRCC, renal cell carcinoma; PFS, progression-free survival; OS, overall survival; PD-1, programmed death-1.
3 Study design and endpoints Randomized, open-labeled phase III study to compare nivolumab with everolimus in patients with advanced RCC after prior systemic therapy (NCT )Enrolled patientsPreviously treated advanced or metastatic clear-cell RCC1 or 2 prior anti- angiogenic treatmentsRandomize 1:1Nivolumab(N = 410)3 mg/kg every 2 weeks intravenousEverolimus(N = 411)10 mg/dayoralTreat until progression or intolerable toxicityTreatment beyond progression was permitted if drug was tolerated and clinical benefit was notedDisease assessmentsEvery 8 weeks from randomization through 12 monthsThen every 12 weeks until progression or treatment discontinuationPrimary endpointOverall survival (OS)
4 Overall survival Median OS, months (95% CI) Nivolumab (N = 410) 25.0 (21.8–NE)Everolimus (N = 411)19.6 (17.6–23.1)36129151821242730330.00.30.10.188.8.131.52.184.108.40.206Overall Survival (Probability)NivolumabEverolimusHR (98.5% CI),0.73 (0.57–0.93) P =MonthsThe risk of death was reduced by 27% in patients in the nivolumab treatment group compared with those in the everolimus groupStudy stopped after planned interim analysis (398 deaths) because assessment by an independent data monitoring committee concluded that the study met its primary endpoint, demonstrating superior OS for nivolumabThis means that patients are more likely to live when treated with nivolumab versus everolimusHR, hazard ratio; NE, not estimable.
5 Objective response rate Patients on nivolumab treatment had a significantly better objective response rate than those on everolimus treatmentThis means that more patients responded to treatment with nivolumab than to treatment with everolimus
6 Treatment-related AEs Grade 3 or 4 treatment-related AEs were less frequent with nivolumab than with everolimus and treatment-related adverse events leading to discontinuation were experienced by fewer patients treated with nivolumabThe most common treatment-related AEs of any grade reported in the nivolumab arm were fatigue (33%), nausea (14%), and pruritus (14%), and in the everolimus arm, fatigue (34%), stomatitis (29%), and anemia (24%)There were no treatment-related deaths in the nivolumab treatment armThis suggests that nivolumab has a favorable safety profile in patients with mRCCAE, adverse event; mRCC, metastatic renal cell carcinoma.
7 Key conclusionsCheckMate 025 met its primary endpoint, demonstrating OS superiority with nivolumab versus everolimusThis is the only phase III trial to demonstrate a survival advantage in previously-treated patients with mRCC versus standard therapyNivolumab was associated with a greater number of objective responses than everolimusThe survival improvement and favorable safety profile demonstrated in this phase III trial provides evidence for nivolumab as a potential new treatment option for previously treated patients with mRCCBased on the positive results of this trial, nivolumab was granted a breakthrough therapy designation from the FDA for advanced RCC, reinforcing the importance of these results in a patient population with large unmet medical need