A phase II pilot study of the efficacy and safety of nivolumab and ipilimumab in T1aN0M0 renal cell carcinoma patients ineligible for surgical treatment.

TPS769 Background: Surgery remains the standard curative-intent therapy for localized renal cell carcinoma (RCC). Thus, systemic therapy for RCC should only be considered in patients who have contraindications to surgery. The phase 3 CheckMate 214 trial showed that a combination of nivolumab and ipilimumab has a significant impact on tumor burden in intermediate- and poor-risk metastatic RCC patients with a complete response rate of 11%. Median time to objective response was 2.8 months. Among all complete responders to nivolumab plus ipilimumab in the intention-to-treat population, 5% achieved a complete response at the first scan. We hypothesize that this combination could eliminate the primary tumor in T1aN0M0 patients ineligible for surgical treatment. Methods: This is a prospective, multicenter, non-randomized phase 2 pilot study. Patients with biopsy-proven clear-cell RCC of ≤4 cm (cT1a), no evidence of any metastases, and unable to have surgery or other nephron-sparing interventions (ablation) for any reason (functional single kidney with a central, high-complexity RCC, high risk of nephrectomy and dialysis, patients with complex coagulation disorders, etc.) or with preference to have no surgery or intervention for any reason will receive combination of ipilimumab (1 mg/kg intravenously) every 3 weeks for four doses, and nivolumab (240 mg intravenously) every 2 weeks during 16 weeks. The primary endpoint is complete response rate. Simon's two-stage design (Simon, 1989) is used. The null hypothesis that the true complete response rate is 11% will be tested against a one-sided alternative. This design yields a type I error rate of 0.05 and power of 0.9 when the true complete response rate is 60% (alternative hypothesis). In the first stage, 3 patients will be accrued. If there are no complete responses in these 3 patients, the study will be stopped. Otherwise, 5 additional patients will be accrued for a total of 8. The null hypothesis will be rejected if 3 or more responses are observed in 8 patients. Clinical trial information: NCT04134182.

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Durable complete response to combination nivolumab and ipilimumab in metastatic renal cell carcinoma

Trends in Immunotherapy ◽

10.24294/ti.v6.i1.1387 ◽

2022 ◽

Vol 6 (1) ◽

Author(s):

Kenta Takayasu ◽

Koei Muguruma ◽

Hidefumi Kinoshita

Keyword(s):

Renal Cell Carcinoma ◽

Combination Therapy ◽

Cell Carcinoma ◽

Renal Cell ◽

Response Rate ◽

Checkpoint Inhibitors ◽

Cancer Recurrence ◽

Complete Response ◽

Durable Response ◽

Durable Complete Response

Immune checkpoint inhibitors, which promote or suppress the anti-tumor immune response, are becoming the mainstay of cancer treatment. In 2018, CheckMate 214 study showed a higher response rate with ipilimumab and nivolumab combination therapy compared to conventional therapy for advanced renal cell carcinoma. We report a case of complete response and durable response for two years to ipilimumab and nivolumab combination therapy in a patient with postoperative renal cancer recurrence that caused immune-related adverse events such as interstitial pneumonia and hepatotoxicity.

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Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma: Results of overall survival for CALGB 90206

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.18_suppl.lba5019 ◽

2009 ◽

Vol 27 (18_suppl) ◽

pp. LBA5019-LBA5019 ◽

Cited By ~ 23

Author(s):

B. I. Rini ◽

S. Halabi ◽

J. Rosenberg ◽

W. M. Stadler ◽

D. A. Vaena ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Interferon Alpha ◽

Renal Cell ◽

Objective Response Rate ◽

Response Rate ◽

Objective Response ◽

Phase Iii ◽

Type I

LBA5019 Background: Bevacizumab (BEV) plus interferon alpha (IFN) demonstrated a superior objective response rate and progression-free survival (PFS) versus IFN monotherapy in renal cell carcinoma (RCC) patients in 2 phase III trials. The primary objective of CALGB 90206 was to compare overall survival (OS) for advanced RCC patients receiving BEV plus IFN or IFN alone. Methods: Patients with previously-untreated, metastatic RCC with a clear cell component and Karnofsky performance status of ≥ 70% were eligible. Patients were prospectively randomized to receive BEV (10 mg/kg intravenously every 2 weeks) plus IFN (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN as monotherapy. Randomization was stratified by nephrectomy status and number of MSKCC adverse features. The primary endpoint was OS, defined as the time from randomization to death due to any cause. The trial was designed with 86% power to detect a hazard ratio (HR) of 0.76, assuming a two-sided type I error of 0.05. The primary analysis was an intent-to-treat approach using the stratified log-rank statistic, and the present analysis was based on the target number of 588 deaths. Results: Between October 2003 and July 2005, 732 patients were enrolled; 369 pts to BEV plus IFN and 363 pts to IFN monotherapy. The median duration of follow up among censored patients was 46.2 months (IQR=45.2–48.2). The median OS was 18.3 months (95% CI; 16.5–22.5) for BEV plus IFN and 17.4 months (95% CI; 14.4–20.0, unstratified log rank p = 0.097) for IFN monotherapy. The stratified HR was 0.86 (95% CI; 0.73–1.01) for BEV plus IFN compared to IFN (stratified log-rank p = 0.069). The median OS for BEV plus IFN versus IFN was 32.5 vs. 33.5 months (p = 0.524) for MSKCC good risk, 17.7 vs. 16.1 months (p = 0.174) for intermediate risk and 6.6 vs. 5.7 months (p = 0.245) for poor risk patients. The median PFS was 8.4 months vs. 4.9 months (p<0.0001). Fifty-three percent of patients received subsequent systemic therapy. Conclusions: The addition of BEV to IFN significantly improves the objective response rate and PFS versus IFN monotherapy. Overall survival favored the BEV plus IFN arm, not meeting pre-defined criteria for significance. [Table: see text]

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Brain Complete Response to Cabozantinib prior to Radiation Therapy in Metastatic Renal Cell Carcinoma

Case Reports in Urology ◽

10.1155/2019/6769017 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

An Uche ◽

Chad Sila ◽

Tad Tanoura ◽

James Yeh ◽

Neil Bhowmick ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Radiation Therapy ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitor ◽

Complete Response ◽

Heavily Pretreated ◽

Treatment Paradigm ◽

Endothelial Growth Factor

Cabozantinib represents an established vascular endothelial growth factor- (VEGF-) tyrosine kinase inhibitor (TKI) in the treatment paradigm of metastatic renal cell carcinoma (mRCC). Its activity in mRCC patients with brain metastases (BMs) has been largely underreported in prospective clinical trials. We present the unique case of a heavily pretreated mRCC patient with BMs who achieved a brain complete response to cabozantinib prior to receiving radiation therapy. We end with a literature review and discussion of the biologic rationale and growing evidence supporting the intracranial activity of cabozantinib.

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Preliminary Exploration of Tolerability in Preoperative Stereotactic Ablation Radiotherapy Combined with Surgical Treatment for Renal Cell Carcinoma and Inferior Vena Cava Tumor Thrombus

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2019.06.1955 ◽

2019 ◽

Vol 105 (1) ◽

pp. E256

Author(s):

Z. Liu ◽

R. Peng ◽

H. Wang ◽

L. Ma ◽

J. Wang

Keyword(s):

Renal Cell Carcinoma ◽

Surgical Treatment ◽

Inferior Vena Cava ◽

Cell Carcinoma ◽

Renal Cell ◽

Tumor Thrombus ◽

Inferior Vena ◽

Vena Cava

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Can Tyrosine Kinase Inhibitors be Discontinued in Patients with Metastatic Renal Cell Carcinoma and a Complete Response to Treatment? A Multicentre, Retrospective Analysis

European Urology ◽

10.1016/j.eururo.2008.10.021 ◽

2009 ◽

Vol 55 (6) ◽

pp. 1430-1439 ◽

Cited By ~ 69

Author(s):

Manfred Johannsen ◽

Anne Flörcken ◽

Axel Bex ◽

Jan Roigas ◽

Marco Cosentino ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Tyrosine Kinase ◽

Cell Carcinoma ◽

Retrospective Analysis ◽

Tyrosine Kinase Inhibitors ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitors ◽

Complete Response ◽

Response To Treatment

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Renal Cell Carcinoma with Synchronous Metastasis to the Calcaneus and Metachronous Metastases to the Ovary and Gallbladder

Case Reports in Medicine ◽

10.1155/2011/671645 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4 ◽

Cited By ~ 11

Author(s):

Jasper Decoene ◽

Filip Ameye ◽

Evelyne Lerut ◽

Raymond Oyen ◽

Hein Van Poppel ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Surgical Treatment ◽

Cell Carcinoma ◽

Renal Cell ◽

Review Of The Literature ◽

Synchronous Metastasis ◽

Renal Cell Carcinomas ◽

Gallbladder Metastasis ◽

Metachronous Metastases ◽

Systemic Therapies

Renal cell carcinomas (RCCs) are known for their unpredictable metastatic pattern. We present the case of a 63-year-old woman who initially presented in 1992 with a metastasis in the left calcaneus that led to the discovery of RCC. In 1998, a new metastasis was found in the ovary. In 2008, the diagnosis of a gallbladder metastasis was made. All metastases were surgically removed; no additional systemic therapies were used. Aggressive surgical treatment can prolong the survival of patients with resectable metastases. Patterns of metastasis are discussed, and a brief review of the literature is given regarding each localization.

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