Efficacy of cabozantinib (C) after PD-1/PD-L1 checkpoint inhibitors in metastatic renal cell carcinoma (mRCC): The Gustave Roussy experience

Derosa, Lisa; Rouche, Julia Arfi; Colomba, Emeline; Baciarello, Giulia; Routy, Bertrand; Albigès, Laurence; Escudier, Bernard

doi:10.1093/annonc/mdx371.030

Cited by 10 publications

(5 citation statements)

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“…For the latter subgroup, cabozantinib was associated with improved PFS (HR 0.22; 95% CI 0.07-0.65), OS (HR 0.56; 95% CI 0.21-1.52), and ORR (22% vs. 0%) compared with everolimus [10]. Small retrospective studies further support cabozantinib activity after progression on PD-1/PD-L1 checkpoint inhibitors, showing ORR ranging from 33 to 42% [11][12][13].…”

Section: Discussionmentioning

confidence: 83%

Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis

et al. 2020

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Background Angiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy. Objective To describe the outcome of cabozantinib in patients previously treated with immunotherapy. Patients and methods Patients with mRCC who received cabozantinib immediately after nivolumab were included. The primary endpoint was to assess the outcome in terms of efficacy and activity. Results Eighty-four mRCC patients met the criteria to be included in the final analysis. After a median follow-up of 9.4 months, median overall survival was 17.3 months. According to the IMDC criteria, the rates of patients alive at 12 months in the good, intermediate, and poor prognostic groups were 100%, 74%, and 33%, respectively (p < 0.001). The median progression-free survival (PFS) was 11.5 months (95% CI 8.3-14.7); no difference was found based on duration of previous first-line therapy or nivolumab PFS. The overall response rate was 52%, stable disease was found as the best response in 25.3% and progressive disease in 22.7% of patients. Among the 35 patients with progressive disease on nivolumab, 26 (74.3%) patients showed complete/partial response or stable disease with cabozantinib as best response after nivolumab. The major limitations of this study are the retrospective nature and the short follow-up. Conclusions Cabozantinib was shown to be effective and active in patients previously receiving immune checkpoint inhibitors. Therefore, cabozantinib can be considered a valid therapeutic option for previously treated mRCC patients, irrespective of the type and duration of prior therapies.Giampaolo Tortora and Giuseppe Procopio share the co-last authorship.

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Section: Discussionmentioning

confidence: 83%

Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis

et al. 2020

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“…Cabozantinib is active after previous TKI failure and its pivotal trial only included a few patients with prior immunotherapy (Table 3). Additional evidence supports the idea that cabozantinib is active after prior checkpoint-inhibitor therapy, which also applies to other TKIs [55,[59][60][61][63][64][65].…”

Section: Discussionsupporting

confidence: 57%

“…In Table 3 we summarized important results of relevant trials in which different single agents or combinations were evaluated in second-line therapy [50][51][52][53][54]. Data for TKIs after failure of immunotherapies in second [55][56][57][58][59][60] or later lines [61][62][63][64][65][66] remains scarce (Table 3). Even recent randomized controlled studies only included a minority of patients after combinations of immunotherapies in first line [67].…”

Section: Second-line Treatment Optionsmentioning

confidence: 99%

Consensus paper: current state of first- and second-line therapy in advanced clear-cell renal cell carcinoma

et al. 2020

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The therapy of advanced (clear-cell) renal cell carcinoma (RCC) has recently experienced tremendous changes. Several new treatments have been developed, with PD-1 immune-checkpoint inhibition being the backbone of therapy. Diverse immunotherapy combinations change current first-line standards. These changes also require new approaches in subsequent lines of therapy. In an expert panel, we discussed the new treatment options and how they change clinical practice. While first-line immunotherapies introduce a new level of response rates, data on second-line therapies remains poor. This scenario poses a challenge for clinicians as guideline recommendations are based on historical patient cohorts and agents may lack the appropriate label for their in guidelines recommended use. Here, we summarize relevant clinical data and consider appropriate treatment strategies.

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“…There is no consensus on optimal treatment sequencing in ccRCC. Cabozantinib has been shown to be effective after treatment with immunotherapy or TKIs and is a preferred second-line therapy [11,12,[22][23][24][81][82][83]. Nivolumab is also a preferred second-line therapy and has been shown to be effective after prior sunitinib, pazopanib, or IL-2 [22][23][24]83,84].…”

Section: Treatment Sequencingmentioning

confidence: 99%

Current and emerging therapies for first-line treatment of metastatic clear cell renal cell carcinoma

Atkins¹,

Tannir

2018

Cancer Treatment Reviews

307

238

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There has been significant progress in the treatment of patients with advanced clear cell renal cell carcinoma (ccRCC), with improved knowledge of disease biology and the introduction of targeted agents and immunotherapies. In this review, we discuss current and emerging first-line treatment options, including recent approvals of the tyrosine kinase inhibitor (TKI) cabozantinib and the immunotherapy combination of nivolumab (anti-programmed cell death 1 [PD-1])/ipilimumab (anti-cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4]), and initial outcomes with the combination of atezolizumab (anti-PD-ligand 1 [PD-L1])/bevacizumab (anti-vascular endothelial growth factor [VEGF]). Key clinical data are reviewed, as these novel first-line treatments offer significant improvement, particularly for patients classified as intermediate/poor risk for whom previously available therapies have demonstrated limited efficacy. Treatment recommendations based on clinical evidence and expert opinion are discussed. We also review ongoing studies investigating combinations of checkpoint inhibitors with TKIs, including cabozantinib and axitinib, and with other novel immunomodulatory agents, and the potential role of single-agent immunotherapy for select patients. With a growing treatment armamentarium, identification and validation of biomarkers will be crucial for optimizing first-line selection and treatment sequences.

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Efficacy of cabozantinib (C) after PD-1/PD-L1 checkpoint inhibitors in metastatic renal cell carcinoma (mRCC): The Gustave Roussy experience

Cited by 10 publications

References 0 publications

Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis

Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis

Consensus paper: current state of first- and second-line therapy in advanced clear-cell renal cell carcinoma

Current and emerging therapies for first-line treatment of metastatic clear cell renal cell carcinoma

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