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

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.

scholarly journals Pathologic Complete Response to Neoadjuvant Nivolumab/Ipilimumab in a Patient with Metastatic Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Taylor C. Peak ◽  
Elena M. Fenu ◽  
Michael B. Rothberg ◽  
Christopher Y. Thomas ◽  
Ronald L. Davis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Durable Response ◽  
Effective Combination ◽  
The Face

Nivolumab plus ipilimumab represents an effective combination of checkpoint inhibitors that can lead to a durable response with minimal toxicity in patients with metastatic renal cell carcinoma (mRCC). We present a case of a pathologic complete response to neoadjuvant nivolumab plus ipilimumab in a patient with a 13.9 cm left renal mass and significant retroperitoneal and iliac lymphadenopathy, classified as intermediate-risk mRCC. We discuss and review the literature on complete responses after systemic therapy and the ability to predict who has undergone a complete response in the face of residual radiographic evidence of disease.

Clinical, pathologic, and genomic profiles of exceptional responders to anti−PD1 therapy in renal cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 625-625 ◽  
Author(s):  
Mark Wayne Ball ◽  
Michael Hiroshi Johnson ◽  
Michael A. Gorin ◽  
Maria Rodriguez ◽  
Luis A. Diaz ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Somatic Mutations ◽  
Complete Response ◽  
Response To Therapy ◽  
Rna Expression ◽  
Refractory Disease ◽  
Durable Response ◽  
Durable Complete Response

625 Background: Previous studies have correlated response to PD−1 blockade with PD−L1 over−expression, as well as cell−mediated immune transcripts). However, factors associated with long−term, durable response to nivolumab in patients with RCC have not yet been elucidated. To better understand these factors, we conducted a study to characterize the two extremes of response to therapy – exceptional responders who had durable, complete response and patients who had primary refractory disease. Methods: Patients with durable, complete response (“exceptional responders”) (n=4) and primary refractory disease (n=3) were analyzed. Immunohistochemical staining for PD−L1, CD8 and FOXP3, whole−exome sequencing and quantitative RNA expression profiling was performed and correlated with clinical outcomes. Results: Exceptional responders had trends toward greater CD8+ lymphocyte infiltrate (126.7 vs 28.8 lymphocytes/hpf), higher number of somatic mutations (67 vs 35 somatic mutations/genome), and higher number of predicted mutation associated neoantigens than primary refractory patients (44 vs 8). Expression analysis demonstrated acute phase and immune tolerance signatures in primary refractory patients, while exceptional responders had higher expression of T cell and innate immune signatures. Conclusions: Exceptional responders and primary refectory patients have distinct pathologic, genomic and RNA expression profiles. Larger studies are needed to fully elucidate the basis of response to PD−1 blockade in patients with renal cell carcinoma.

Cabozantinib versus other TKIs after CPI treatment in the real-world management of patients with metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 293-293
Author(s):  
Florence Marteau ◽  
Brooke Harrow ◽  
Christine McCarthy ◽  
Joel Wallace ◽  
Alisha Monnette ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
P Value ◽  
The Real ◽  
The Us

293 Background: Checkpoint inhibitors (CPIs) are a treatment option for patients with metastatic renal cell carcinoma (mRCC), but there is limited clinical data on the efficacy of targeted therapies following CPI treatment. Cabozantinib is a tyrosine kinase inhibitor (TKI) that targets multiple receptor kinases implicated in tumorigenesis. In the US, cabozantinib is approved for use in patients with advanced RCC including after CPI treatment. Methods: This retrospective observational cohort study (NCT04353765) evaluated outcomes associated with cabozantinib or other TKIs (axitinib, lenvatinib, pazopanib, sorafenib, sunitinib) in patients with mRCC following CPI treatment. Eligible patients initiated TKI therapy between May 1, 2016 and Sep 31, 2019 and had received a CPI as their last systemic treatment prior to TKI therapy. Patients were identified from the US Oncology Network iKnowMed electronic health record database through structured queries and a targeted chart review. The following real-world outcomes were assessed: 6-month response rate (RR6months; primary); overall response rate (ORR); overall survival (OS); time to treatment discontinuation (TTD); rates of dose reductions, and discontinuation due to adverse events (AEs). The p value for RR6months was used to test for non-inferiority. Results: Eligible patients ( n = 247) had a mean (SD) age of 65.9 (10.5) years and 74.1% were male; 75.7% ( n = 187) received cabozantinib and 24.3% ( n = 60) received other TKIs. All patients had intermediate or poor MSKCC score; more poor-risk patients received cabozantinib than other TKIs (28.9% vs 20%). Outcomes data are shown in the Table. Compared with other TKIs, cabozantinib was associated with a significantly higher RR6months and ORR, and TTD was twice as long with cabozantinib. Discontinuation due to AEs was more frequent with other TKIs than with cabozantinib, although this was not statistically significant; 21.7% of discontinuations occurred during the first 3 months of treatment. AEs leading to discontinuation were consistent with the known safety profile of the products. Conclusions: In this mRCC population receiving routine care in the US, cabozantinib was used more frequently than other TKIs after CPI treatment. Cabozantinib was an effective and well tolerated option post-CPI, with a high response rate in the real-world setting.abozantinib was associated with a significantly higher response rate and a lower discontinuation rate due to AEs; TTD was double that of other TKIs. [Table: see text]

scholarly journals Stereotactic body radiation therapy in combination with systemic therapy for metastatic renal cell carcinoma: a prospective multicentre study

ESMO Open ◽  
2019 ◽  
Vol 4 (5) ◽  
pp. e000535 ◽  
Author(s):  
Natalia Dengina ◽  
Timur Mitin ◽  
Sergey Gamayunov ◽  
Sufia Safina ◽  
Yuliya Kreinina ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Complete Response ◽  
Lesion Size ◽  
Target Lesion

BackgroundTyrosine kinase inhibitors (TKIs) and checkpoint inhibitors have been established as effective treatment for metastatic renal cell carcinoma (mRCC), but only a minority of patients achieve complete response. Additional strategies are necessary to improve these agents’ efficacy.MethodsPatients with stable disease for at least 4 months on TKI or checkpoint inhibitors were included. Stereotactic body radiotherapy (SBRT) was delivered to an organ with comparable lesions, where one lesion was in the treatment target and the other one was intentionally left untreated (control lesion). Response in both lesions was scored using the Response Evaluation Criteria in Solid Tumors V.1.1 criteria 2 months after completion of SBRT. The primary endpoint was the rate of SBRT adverse events, and the secondary endpoints included the rate of reduction in target lesion size.Results17 patients were enrolled (14 men and 3 women, median age: 54.5 years old). SBRT was delivered to the lungs (n=5), bones (n=4), lymph nodes (n=4), liver (n=1), primary renal cell carcinoma (RCC) (n=1) and locally recurrent RCC (n=2). The equivalent dose in 2 Gy with an alpha to beta ratio of 2.6 was 114 Gy. With a median follow-up of 8 months, the cumulative rate of SBRT-related toxicity (grade 1) was 12% (n=2), consisting of oesophagitis and skin erythema. No grade 2 or higher toxicity was detected. Radiographic response in the target lesion was seen in 13 patients (76%), with complete response in 5 (29%) patients and partial response in 8 (47%), including abscopal effect in 1 patient. Control lesions remained stable in 16 patients. The difference between response in the target and control lesions as judged by the mean sizes of these lesions before and at 2 months after SBRT was statistically significant (p<0.01). Fraction size of 10 Gy or greater was associated with complete response (p<0.01).ConclusionExtracranial SBRT in patients with mRCC treated with TKI or checkpoint inhibitors is well tolerated and could be effective.Trial registration numberNCT02864615

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

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS769-TPS769
Author(s):  
Ilya Tsimafeyeu ◽  
Maria Volkova ◽  
Rustem Airatovich Gafanov ◽  
Dmitry Nosov ◽  
Axel Bex
Keyword(s):  
Renal Cell Carcinoma ◽  
Surgical Treatment ◽  
Pilot Study ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Null Hypothesis ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Type I

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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