scholarly journals Survival outcomes and independent response assessment with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma: 42-month follow-up of a randomized phase 3 clinical trial

2020 ◽  
Vol 8 (2) ◽  
pp. e000891 ◽  
Author(s):  
Robert J Motzer ◽  
Bernard Escudier ◽  
David F McDermott ◽  
Osvaldo Arén Frontera ◽  
Bohuslav Melichar ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Complete Response ◽  
Intermediate Risk ◽  
First Line ◽  
Phase 3 ◽  
Poor Risk ◽  
Risk Patients

BackgroundThe extent to which response and survival benefits with immunotherapy-based regimens persist informs optimal first-line treatment options. We provide long-term follow-up in patients with advanced renal cell carcinoma (aRCC) receiving first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the phase 3 CheckMate 214 trial. Survival, response, and safety outcomes with NIVO+IPI versus SUN were assessed after a minimum of 42 months of follow-up.MethodsPatients with aRCC were enrolled from October 16, 2014, through February 23, 2016. Patients stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and region were randomized to nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks for four doses, followed by nivolumab (3 mg/kg) every 2 weeks; or SUN (50 mg) once per day for 4 weeks (6-week cycle). Primary endpoints: overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) per independent radiology review committee in IMDC intermediate-risk/poor-risk patients. Secondary endpoints: OS, PFS, and ORR in the intention-to-treat (ITT) population and safety. Favorable-risk patient outcomes were exploratory.ResultsAmong ITT patients, 550 were randomized to NIVO+IPI (425 intermediate/poor risk; 125 favorable risk) and 546 to SUN (422 intermediate/poor risk; 124 favorable risk). Among intermediate-risk/poor-risk patients, OS (HR, 0.66; 95% CI, 0.55–0.80) and PFS (HR, 0.75; 95% CI, 0.62–0.90) benefits were observed, and ORR was higher (42.1% vs 26.3%) with NIVO+IPI versus SUN. In ITT patients, both OS benefits (HR, 0.72; 95% CI, 0.61–0.86) and higher ORR (39.1% vs 32.6%) were observed with NIVO+IPI versus SUN. In favorable-risk patients, HR for death was 1.19 (95% CI, 0.77–1.85) and ORR was 28.8% with NIVO+IPI versus 54.0% with SUN. Duration of response was longer (HR, 0.46–0.54), and more patients achieved complete response (10.1%–12.8% vs 1.4%–5.6%) with NIVO+IPI versus SUN regardless of risk group. The incidence of treatment-related adverse events was consistent with previous reports.ConclusionsNIVO+IPI led to improved efficacy outcomes versus SUN in both intermediate-risk/poor-risk and ITT patients that were maintained through 42 months’ minimum follow-up. A complete response rate >10% was achieved with NIVO+IPI regardless of risk category, with no new safety signals detected in either arm. These results support NIVO+IPI as a first-line treatment option with the potential for durable response.Trial registration numberNCT02231749.

Subclassification of the intermediate-risk group in patients with advanced renal cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16537-e16537
Author(s):  
Maria Zapata-Garcia ◽  
Maria Zurera Berjaga ◽  
Alba Moratiel Pellitero ◽  
Marta Gascon Ruiz ◽  
Andrea Sesma Goñi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Intermediate Risk ◽  
First Line ◽  
Poor Risk ◽  
Prognosis Group

e16537 Background: Renal cell carcinoma (RCC) have low prevalence but it incidence is increasing. For a correct therapeutic approach, it is important to carry out a correct prognostic stratification. Several prognostication systems have been proposed. One of the most commonly used is the one developed by Heng. It is based on IMDC database. This classification includes six prognostic factors (hemoglobin, neutrohils, platelets, serum calcium, Karnosky Performance Status and time from diagnosis to initiaton treatment) to divide patients into three gorups. The relevance of IMDC prognostic criterio, in the era of immunotherapy, remains to be established. In the absence of alternative criteria, these prognostication system continue to be used. A great prognostic disparity has been observed in the intermediate prognosis group. This raises the need to divide this group into two. Thus, patients included in it would be better selected. Methods: Observational, single-center, retrospective study, based on a cohort of 107 patients with advanced RCC, recruited from January 2006 to December 2019. Main objective: Evaluate whether survival of patients with intermediate prognosis (treated with antiangiogenic in first-line) is different depending on the presence of one or two prognostic factors. Descriptive and survival analysis (OS and PFS) were performed. In addition, the influence of prognostic factors on OS and PFS were compared using the log-rank test and Cox regression. Results: In the overall population, median overall survival (OS) was 26.86 months (95% CI: 21.09-32.63) and median PFS was 18.41 months (95% CI: 14.02-22.79). Median OS were, in favorable-risk 42.24 months (95% CI: 29.62-54.62), in intermediate-risk 27,24 (95% CI: 19.44-35-03) and in poor-risk 8.00 (95% CI: 4.54-11.45). Median PFS were in favorable-risk 30.53 months (95% CI:20.92-40.13), in intermediate-risk 17,16 (95% CI:11.54-22.78) and poor-risk 6.13 (95% CI:3.02-9.25). Median OS and PFS, in patients with intermediate-risk, with a single risk factor were 33.79 (95% CI 23.17-44.41) and 20.97 months (95% CI 13.35-28.59), compared to 14.88 (95% CI 8.80-20.95) and 10.59 months (95% CI 4.87-16.32) in those with two risk factors. The results were statistically significant in OS (p = 0.01) and PFS (p = 0.037). Conclusions: The differences in median OS and PFS, within the intermediate prognosis group (1 or 2 RF), confirm the existence of two subgroups of patients. Patients with 1 RF are similar to those with favorable-risk. These results are important since, the presence of 1 or 2 RF, would condition the choice of TKIs as part of the first-line treatment combination. More studies are needed to better subclassify the intermediate risk group when optimizing the best treatments for each patient.

scholarly journals What is the optimum systemic treatment for advanced/metastatic renal cell carcinoma of favourable, intermediate and poor risk, respectively? A systematic review and network meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e034626
Author(s):  
Guanghui Cao ◽  
Xiaoqiang Wu ◽  
Zhiwei Wang ◽  
Xiangyong Tian ◽  
Chan Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Intermediate Risk ◽  
Optimum Treatment ◽  
Poor Risk ◽  
Risk Patients ◽  
Metastatic Rcc ◽  
Systemic Therapies

PurposeThe optimum systemic therapies for advanced/metastatic renal cell carcinoma (RCC) of favourable, intermediate and poor risk have not been established. We aimed to compare and rank the effects associated with systemic therapies in the first-line setting.MethodsWe searched PubMed, Cochrane databases, Web of Science and ClinicalTrials.gov for randomised controlled trials (RCT) published up to February 2020 of all available treatments for advanced/metastatic RCC. Analysis was done on a Bayesian framework.Results15 unique RCTs including 8995 patients were identified. For advanced/metastatic RCC of favourable risk, avelumab plus axitinib was associated with a significantly higher improvement in progression-free survival (PFS) than sunitinib (HR 0.57, 95% CI 0.34 to 0.96). For intermediate-risk patients, cabozantinib, nivolumab plus ipilimumab, pembrolizumab plus axitinib and avelumab plus axitinib were associated with significantly higher improvement in PFS than sunitinib (HR 0.63, 95% CI 0.44 to 0.97; HR 0.66, 95% CI 0.53 to 0.81; HR 0.58, 95% CI 0.44 to 0.80; HR 0.62, 95% CI 0.47 to 0.83, respectively); pembrolizumab plus axitinib and nivolumab plus ipilimumab were associated with significantly higher improvement in overall survival (OS) than sunitinib (HR 0.53, 95% CI 0.34 to 0.81; HR 0.66, 95% CI 0.50 to 0.87, respectively). For poor-risk patients, nivolumab plus ipilimumab and pembrolizumab plus axitinib were associated with significantly higher improvement in PFS than sunitinib (HR 0.57, 95% CI 0.43 to 0.76; HR 0.48, 95% CI 0.30 to 0.82, respectively); nivolumab plus ipilimumab and pembrolizumab plus axitinib were significantly more efficacious for OS than sunitinib (HR 0.57, 95% CI 0.39 to 0.883; HR 0.43, 95% CI 0.23 to 0.80, respectively). For OS, there were 81% and 78% probabilities that pembrolizumab plus axitinib was the best option for intermediate-risk and poor-risk patients, respectively.ConclusionAvelumab plus axitinib might be the optimum treatment for advanced/metastatic RCC of favourable risk. Pembrolizumab plus axitinib might be the optimum treatment for intermediate-risk and poor-risk patients.

scholarly journals First‐line pazopanib in intermediate‐ and poor‐risk patients with metastatic renal cell carcinoma: Final results of the FLIPPER trial

2020 ◽  
Vol 148 (4) ◽  
pp. 950-960
Author(s):  
Michael Staehler ◽  
Andrej Panic ◽  
Peter J. Goebell ◽  
Marie Merling ◽  
Karin Potthoff ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
First Line ◽  
Poor Risk ◽  
Risk Patients

scholarly journals Nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma: analysis of Japanese patients in CheckMate 214 with extended follow-up

2019 ◽  
Vol 50 (1) ◽  
pp. 12-19 ◽  
Author(s):  
Yoshihiko Tomita ◽  
Tsunenori Kondo ◽  
Go Kimura ◽  
Takamitsu Inoue ◽  
Yoshiaki Wakumoto ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Safety Profile ◽  
Renal Cell ◽  
Objective Response ◽  
Japanese Patients ◽  
Advanced Renal Cell Carcinoma ◽  
Poor Risk ◽  
Risk Patients

Abstract Background Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients. Methods CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-to-treat (ITT) patients and safety (ITT patients). Results Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months’ minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19–1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62–2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3–4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%). Conclusions Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed. https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.

Efficacy of nivolumab/ipilimumab in patients with initial or late progression with nivolumab: Updated analysis of a tailored approach in advanced renal cell carcinoma (TITAN-RCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4576-4576
Author(s):  
Marc-Oliver Grimm ◽  
Emilio Esteban ◽  
Philippe Barthélémy ◽  
Manuela Schmidinger ◽  
Jonas Busch ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Remission Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Poor Risk ◽  
Secondary Endpoints ◽  
Tailored Approach

4576 Background: TITAN-RCC uses a tailored immunotherapy approach in renal cell carcinoma (RCC), starting with nivolumab (nivo) induction followed by nivo + ipilimumab (ipi) as immunotherapeutic “boost” in non-responders. Patients with initial partial or complete response (PR/CR) continued with nivo maintenance but received later “boosts” for progressive disease (PD). Here we report updated results focusing on the efficacy of nivo+ipi in patients with initial PD vs. initial responders with later PD. Methods: Patients with IMDC intermediate and poor risk advanced clear cell RCC were recruited between OCT 2016 and DEC 2018. Patients started with nivo 240 mg Q2W induction. Patients with early significant PD (week 8) or non-responders at week 16 received 2-4 nivo+ipi “boost” cycles. Responders (PR/CR) to nivo monotherapy continued with maintenance but could receive nivo+ipi for later PD. The primary endpoint is confirmed investigator assessed objective response rate (ORR) per RECIST in first line (1L) and second line (2L). Secondary endpoints included activity of nivo monotherapy, remission rate with nivo+ipi “boost”, safety and overall survival (OS). Results: 109 1L and 98 2L (after TKI) patients were analyzed for efficacy. Median age was 65 years (range 20-87). 71 % were intermediate and 25 % poor risk. Confirmed ORR with nivo monotherapy was 28 % for 1L and 17 % for 2L. After a median follow-up of 12.8 months best overall response after nivo induction ± nivo+ipi was 36 % in 1L and 30 % in 2L. Of all patients, 38 received nivo+ipi for stable disease (SD) up to week 16, with 1 (3 %), 4 (11 %) and 26 (68 %) achieving CR, PR and SD, respectively. 28 patients in 1L and 43 in 2L were boosted with nivo+ipi for initial PD. Of these, 3 (11 %) and 8 (29 %) achieved PR and SD, respectively, in 1L, whereas 3 (7.0 %) achieved CR, 6 (14 %) PR and 13 (30 %) SD in 2L. 16 and 10 patients received “boosts” later than week 16 for PD during nivo maintenance in 1L and 2L, respectively. Thereof, 3 (19 %) achieved PR and 5 (31 %) SD in 1L, whereas 2 (20 %) achieved PR and 3 (30 %) SD in 2L. Progression-free survival was 6.3 months (95 % CI 3.7 – 10.1) and 3.7 months (95 % CI 2.0 - 4.5) in 1L and 2L, respectively. OS was 27.2 months (95 % CI 19.9 – not estimable (NE)) in 1L and 20.2 months (95 % CI 15.6 – NE) in 2L. Treatment-related adverse events will be presented. Conclusions: Our tailored approach with nivo+ipi “boosts” results in improved response rates compared to nivo monotherapy. Our updated analysis suggests that almost half of the patients receiving “boosts” for PD improve to either PR/CR (18 %) or SD (30 %), irrespective of initial or later progression with nivo. Clinical trial information: NCT02917772. [Table: see text]

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