Related Experiment Video
Updated: Dec 30, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025
Bernard Escudier1, Robert J Motzer2, Padmanee Sharma3
1Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Background:
Response patterns to nivolumab differ from those seen with other approved targeted therapies.
Objective:
To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond (Response Evaluation Criteria In Solid Tumors) RECIST progression.
Design, Setting, And Participants:
This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study. Patients continuing to tolerate therapy and exhibiting investigator-assessed clinical benefit were eligible to be treated beyond RECIST progression (TBP) and received therapy for ≥4 wk after first progression; patients not treated beyond RECIST progression (NTBP) received 0 wk to <4 wk of therapy after progression.
Interventions:
Nivolumab 3mg/kg intravenously every 2 wk.
Results And Limitations:
Of 406 nivolumab-treated patients, 316 (78%) progressed by RECIST criteria. Of those who progressed, 48% were TBP, 52% were NTBP. Before being TBP, objective response rate (95% confidence interval) was 20% (14-28) and 14% (9-21) in patients TBP and NTBP, respectively. Differences in clinical characteristics assessed at first progression between patients TBP versus NTBP included better Karnofsky performance status, less deterioration in Karnofsky performance status, shorter time to response, lower incidence of new bone lesions, and improved quality of life. Postprogression, 13% of all patients TBP (20/153) had ≥30% tumor burden reduction including patients with preprogression and postprogression tumor measurements (n=142) and complete/partial response (28%, 8/29), stable disease (6%, 3/47), and progressive disease (14%, 9/66) as their best response before being TBP. Incidence of treatment-related adverse events in patients TBP was lower after (59%) versus before (71%) progression. Limitations included potential bias from the nonrandomized nature of the analysis.
Conclusions:
A subset of patients with advanced renal cell carcinoma and RECIST progression experienced tumor reduction postprogression with nivolumab, and had an acceptable safety profile. Clinical judgment remains essential when switching therapy. ClinicalTrials.gov Identifier: NCT01668784.
Patient Summary:
A subset of patients with advanced renal cell carcinoma and disease progression may continue to benefit from nivolumab treatment beyond progression as evidenced by tumor reduction postprogression and an acceptable safety profile.
Insights
Nivolumab demonstrated efficacy in advanced renal cell carcinoma patients treated beyond RECIST progression. A subset experienced tumor reduction and had an acceptable safety profile, suggesting continued benefit.
Area of Science:
- Oncology
- Immunotherapy
- Renal Cell Carcinoma Research
Background:
- Response patterns to nivolumab differ from traditional targeted therapies.
- Advanced renal cell carcinoma (RCC) presents unique treatment challenges.
Purpose of the Study:
- To evaluate nivolumab's efficacy in previously treated advanced RCC patients who continued therapy beyond Response Evaluation Criteria In Solid Tumors (RECIST) progression.
- To analyze clinical characteristics and outcomes of patients treated beyond progression (TBP) versus those not treated beyond progression (NTBP).
Main Methods:
- Subgroup analysis of the phase 3 CheckMate 025 study involving nivolumab.
- Patients were categorized as TBP (≥4 weeks of therapy post-progression) or NTBP (<4 weeks post-progression).
- Comparison of objective response rates, clinical characteristics, and adverse events between TBP and NTBP groups.
Main Results:
- Objective response rate was 20% in TBP patients versus 14% in NTBP patients before treatment beyond progression.
- Patients TBP exhibited better Karnofsky performance status, less deterioration, shorter time to response, fewer new bone lesions, and improved quality of life.
- Post-progression, 13% of TBP patients achieved ≥30% tumor burden reduction; treatment-related adverse events were lower after progression (59%) compared to before (71%).
Conclusions:
- A subset of advanced RCC patients may benefit from continuing nivolumab treatment beyond RECIST progression.
- Tumor reduction and an acceptable safety profile were observed in patients treated beyond progression.
- Clinical judgment is crucial when considering therapy changes in advanced RCC.
More Related Videos
07:29Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
06:15Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Related Concept Videos
02:56Treatment Resistant Cancers
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...