Related Experiment Video
Updated: Jun 19, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Management of Metastatic Renal Cell Carcinoma Following First-Line Immune Checkpoint Therapy Failure: A Systematic
Fausto Petrelli1, Ivano Vavassori2, Mauro Rossitto1
1Oncology Unit, ASST Bergamo Ovest, 24047 Treviglio, BG, Italy.
Introduction:
There is a significant gap in the literature concerning the effective management of second-line therapy for patients with metastatic renal cell carcinoma (RCC) who have received immune checkpoint inhibitors (ICIs). Most of the published articles were small multicenter series or phase 2 studies. To our knowledge, a systematic review that comprehensively outlines the range of treatment options available for patients with metastatic RCC who do not respond to first-line ICIs has not yet been conducted. Our aim was to synthesize evidence on second-line therapies for patients with metastatic RCC after initial treatment with ICIs and to offer recommendations on the best treatment regimens based on the current literature.
Material And Methods:
We conducted a search in PubMed, Embase, and the Cochrane Library on 29 February 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We selected articles that met the predetermined inclusion criteria (written in English, retrospective observational studies, prospective series, and randomized trials reporting second-line therapy for metastatic RCC after failure of ICI-based therapy). Relevant articles were identified in the reference lists. The main endpoint was the overall response rate (ORR), with the median progression-free survival (PFS) and overall survival (OS) as secondary endpoints.
Results:
We included 27 studies reporting the outcomes of 1970 patients. Salvage therapies were classified as targeted therapy (VEGFR TKIs) in 18 studies and ICIs in 8 studies. In studies where TKIs were the second line of choice, the pooled ORR was 34% (95% CI: 30.2-38%). In studies where ICIs, alone or in combination with TKIs, were used as second-line therapies, the ORR was 25.7% (95% CI: 15.7-39.2%). In studies where TKIs and ICIs were the second-line choices, the pooled median PFS values were 11.4 months (95% CI: 9.5-13.6 months) and 9.8 months (95% CI: 7.5-12.7 months), respectively.
Conclusions:
This systematic review shows that VEGFR TKIs and ICIs are effective second-line therapies following an initial treatment with anti-PD(L)1 alone or in combination. The treatment choice should be personalized, taking into account the patient's response to first-line ICIs, the site of the disease, the type of first-line combination (with or without VEGFR TKIs), and the patient's overall condition.
Insights
For metastatic renal cell carcinoma patients progressing on immune checkpoint inhibitors, second-line targeted therapy (VEGFR TKIs) and further immune checkpoint inhibitors (ICIs) show effectiveness. Personalized treatment selection is crucial for optimal outcomes in advanced kidney cancer.
Area of Science:
- Oncology
- Translational Medicine
- Clinical Research
Background:
- Significant gap in literature regarding second-line therapy for metastatic renal cell carcinoma (mRCC) post-immune checkpoint inhibitors (ICIs).
- Limited data from small studies necessitates a comprehensive synthesis of available treatment options.
- Need for evidence-based recommendations for managing mRCC after ICI failure.
Purpose of the Study:
- To systematically review and synthesize evidence on second-line therapies for mRCC following first-line ICI treatment.
- To evaluate the efficacy of targeted therapies (VEGFR TKIs) and further ICIs as salvage options.
- To provide recommendations for personalized second-line treatment selection in mRCC.
Main Methods:
- Systematic literature search of PubMed, Embase, and Cochrane Library following PRISMA guidelines.
- Inclusion of retrospective, prospective, and randomized trials reporting on second-line therapy for mRCC after ICI failure.
- Primary endpoint: Overall Response Rate (ORR); Secondary endpoints: Progression-Free Survival (PFS) and Overall Survival (OS).
Main Results:
- Analysis of 27 studies involving 1970 patients treated with second-line VEGFR TKIs or ICIs.
- Pooled ORR for second-line VEGFR TKIs was 34%; for second-line ICIs (alone or combined with TKIs), ORR was 25.7%.
- Pooled median PFS was 11.4 months for VEGFR TKIs and 9.8 months for ICIs as second-line treatment.
Conclusions:
- Both VEGFR TKIs and ICIs are effective second-line treatments for mRCC after initial ICI therapy.
- Personalized treatment selection is essential, considering patient response, disease characteristics, and prior treatment.
- Individualized approaches are key to optimizing outcomes in advanced renal cell carcinoma management.
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