CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features.

McDermott, David F.; Choueiri, Toni K.; Motzer, Robert J.; Aren, Osvaldo Rudy; George, Saby; Powles, Thomas; Donskov, Frede; Harrison, Michael R.; Cid, Jeronimo Rafael Rafael Rodriguez; Ishii, Yuko; McHenry, M. Brent; Mekan, Sabeen; Rini, Brian I.; Tannir, Nizar M.

doi:10.1200/jco.2019.37.15_suppl.4513

Cited by 82 publications

(55 citation statements)

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“…Open access exploratory analysis of a sRCC cohort also demonstrated response to immunotherapy with an ORR of 56.7% with nivolumab plus ipilimumab (95% CI 43.2% to 69.4%) versus 19.2% (95% CI 9.6% to 32.5%) with sunitinib (p<0.0001). 11 While the data from immunotherapy in sRCC have been encouraging, many patients do not demonstrate a significant response, and responsive patients eventually develop progression. In this case report, we describe a patient with sRCC who had an initial response with ipilimumab and nivolumab, rapid progression on maintenance nivolumab, and subsequent response with rechallenge of ipilimumab.…”

Section: Introductionmentioning

confidence: 99%

Salvage ipilimumab associated with a significant response in sarcomatoid renal cell carcinoma

George¹,

Schmidt²,

Tolat³

et al. 2020

J Immunother Cancer

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BackgroundMetastatic sarcomatoid renal cell carcinoma (sRCC) is an aggressive variant of RCC with generally poor prognosis. Treatment with vascular endothelial growth factor inhibitors or chemotherapy generates only short-lived responses. Recent research has suggested a role for combination checkpoint inhibition as first line treatment for metastatic sRCC. This therapy consists of induction with cytotoxic T-lymphocyte-associated protein 4 inhibitor, ipilimumab, administered with programmed cell death protein 1 (PD-1) inhibitor, nivolumab. After completion of four cycles of combination therapy, single-agent maintenance nivolumab is recommended until progression. Patients who progress on maintenance nivolumab are switched to alternate therapy. Herein, we present a case of a patient with RCC who progressed on maintenance nivolumab who, on retreatment with ipilimumab, demonstrated a significant response In addition, we summarize important findings to support the role of salvage ipilimumab in patients with sRCC.Case presentationA 46-year-old man presented with flank pain and hematuria, the work up of which noted a left kidney mass for which he underwent nephrectomy and was diagnosed with localized sRCC with 60% sarcomatoid differentiation. Within 3 months of nephrectomy, he presented with recurrent flank pain and was diagnosed with recurrence of disease. He was treated with ipilimumab 1 mg/kg and nivolumab 3 mg/kg for four doses and demonstrated a partial response. He was then transitioned to single agent nivolumab maintenance. After 3 months on maintenance therapy, he was noted to have progression of disease. Given prior response to immune check point combination, it was decided to rechallenge the patient with 1 mg/kg ipilimumab. After two doses of ipilimumab and nivolumab combination therapy, the patient was noted to have a partial response. He maintained a response for an additional 9 months and treatment was eventually discontinued due to grade 3 toxicity and progression.ConclusionsThis case report demonstrates the utility of retreatment with ipilimumab as a salvage option for patients progressing on maintenance PD-1 inhibitors in metastatic RCC. Further studies are needed to identify predictors of response and toxicity to this approach, as well as the optimal scheduling of ipilimumab with maintenance nivolumab.

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Section: Introductionmentioning

confidence: 99%

Salvage ipilimumab associated with a significant response in sarcomatoid renal cell carcinoma

George¹,

Schmidt²,

Tolat³

et al. 2020

J Immunother Cancer

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“…In contrast, the ESPN trial and multiple retrospective studies included patients with sarcomatoid features in their metastatic nccRCC cohorts (Table ). In abstracts presented at the 2019 ASCO Annual Meeting, patients with metastatic ccRCC and sarcomatoid features were shown to have exceptional responses to pembrolizumab plus axitinib and nivolumab plus ipilimumab, 59% with 11% CR and 57% with 18% CR, respectively . These reports demonstrate how inclusion of metastatic ccRCC with sarcomatoid features would alter ORRs in analyses of patients with metastatic nccRCC.…”

Section: Outcomes Of Clinical Trials or Retrospective Studies For Patmentioning

confidence: 84%

Potential Roles for PD-1 Inhibition and Cabozantinib in Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma

2019

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“…In the IMmotion151 trial, a study that compared the combination of atezolizumab and bevacizumab versus sunitinib, patients with sRCC had a benefit in PFS with the combination arm (HR 0.56, 95% CI 0.38-0.83) [27]. Moreover, the CheckMate214 trial showed that sRCC had encouraging response rate (57%) with nivolumab plus ipilimumab [28]. These results suggest that immunecheckpoint inhibitors might be a better therapeutic strategy for this subgroup of patients.…”

Section: Discussionmentioning

confidence: 98%

Real-world evidence on first-line treatment for metastatic renal cell carcinoma with non-clear cell and sarcomatoid histologies: are sunitinib and pazopanib interchangeable?

Bonadioa

Velho

Marta

et al. 2019

ecancer

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Introduction: Non-clear cell renal cell carcinoma (nccRCC) and sarcomatoid renal cell carcinoma (sRCC) are underrepresented in clinical trials. Treatment approaches are frequently extrapolated from data of clear cell renal cell carcinoma, in which pazopanib is non-inferior to sunitinib. We aim to compare the effectiveness of first-line sunitinib and pazopanib for nccRCC and sRCC. Methods: We evaluated a retrospective cohort of patients with metastatic nccRCC and sRCC treated with first-line sunitinib or pazopanib at an academic cancer centre. Overall survival (OS), progression-free survival (PFS) and response rate were measured. Kaplan-Meier and log-rank analyses were used for time-to-event data. Cox regression was used for prognostic factors. Results: Fifty-three patients were included; 16 (30.1%) treated with sunitinib and 37 (69.9%) with pazopanib. Forty-six (86.8%) patients had nccRCC and 7 (13.2%) had sRCC. The majority had intermediate or poor International Metastatic Renal-Cell Carcinoma Database Consortium risk (93%). Median PFS was 6.6 months with sunitinib and 4.9 months with pazopanib (HR 1.75; P = 0.078). Treatment with pazopanib was associated with inferior OS in comparison with sunitinib (median OS: 30.4 months versus 8.7 months; HR 2.71, 95% CI 1.31-5.58, P = 0.007). These results were confirmed in subgroup analysis of patients with papillary, chromophobe and MiT family translocation histologies (median OS: 38.7 months versus 14.7 months; HR 3.16, 95% CI 1.20-8.29, P = 0.019). Unclassified and sarcomatoid histologies had inferior OS (median: 6.9 and 1.1 months, respectively) regardless of the treatment used. Conclusion: In this patient cohort, pazopanib was associated with inferior OS in comparison with sunitinib for metastatic nccRCC. Larger trials are ideally warranted to confirm these results.

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CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features.

Cited by 82 publications

References 0 publications

Salvage ipilimumab associated with a significant response in sarcomatoid renal cell carcinoma

Salvage ipilimumab associated with a significant response in sarcomatoid renal cell carcinoma

Potential Roles for PD-1 Inhibition and Cabozantinib in Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma

Real-world evidence on first-line treatment for metastatic renal cell carcinoma with non-clear cell and sarcomatoid histologies: are sunitinib and pazopanib interchangeable?

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