Efficacy of Treatments After Lenvatinib in Patients with Advanced Renal Cell Carcinoma
Justine Panian1, Caiwei Zhong2, Sharon H Choi1
1Division of Hematology Oncology, University of California-San Diego, San Diego, CA, USA.
Background And Objective:
Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) used in the upfront and refractory settings for metastatic renal cell carcinoma (mRCC). However, there are limited data on the efficacy of subsequent TKI therapies after lenvatinib. We investigated the activity of TKI therapies after lenvatinib in patients with mRCC.
Methods:
We conducted a retrospective analysis of data from the International Metastatic RCC Database Consortium (IMDC). Patients who received post-lenvatinib treatment were divided into two cohorts: a second-line cohort after first-line lenvatinib; and a third-line cohort after second-line lenvatinib. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the time to treatment failure (TTF).
Key Findings And Limitations:
Of the 168 patients included, 122 (73%) had clear-cell histology. In the second-line cohort (n = 20), all patients received first-line pembrolizumab + lenvatinib. The ORR was 50% and median TTF was 19.7 mo for first-line treatment. Median follow-up from initiation of second-line treatment was 4.9 mo. The ORR to second-line treatment was 5% (95% confidence interval [CI] 0.2-25%) and median TTF was 5.8 mo (95% CI 1.9-14.9). In the third-line cohort (n = 34), most patients received second-line everolimus + lenvatinib (97%). The ORR was 31% and median TTF was 9.2 mo for second-line therapy. Median follow-up from initiation of third-line treatment was 14.9 mo. The ORR to third-line treatment was 12% (95% CI 3.3-27%) and median TTF was 2.8 mo (95% CI 1.9-7.4).
Conclusions And Clinical Implications:
Our data demonstrate modest activity of TKI-based therapy after exposure to lenvatinib. The results highlight the need for better treatment options for patients who experience progression on lenvatinib-based therapies.
Patient Summary:
Lenvatinib is a type of drug called a tyrosine kinase inhibitor (TKI). It is used to treat metastatic kidney cancer either when first diagnosed or after progression on a previous treatment. There is limited information on how patients respond to a different TKI after receiving lenvatinib. Our results show that other TKIs have modest clinical activity after patients have received lenvatinib.
Insights
Subsequent tyrosine kinase inhibitor (TKI) therapies after lenvatinib in metastatic renal cell carcinoma (mRCC) showed modest activity. Further research is needed to identify more effective treatment options for patients progressing on lenvatinib-based therapies.
Area of Science:
- Oncology
- Pharmacology
Background:
- Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) used for metastatic renal cell carcinoma (mRCC).
- Limited data exist on the efficacy of subsequent TKI therapies following lenvatinib treatment.
Purpose of the Study:
- To investigate the activity of tyrosine kinase inhibitor (TKI) therapies in patients with metastatic renal cell carcinoma (mRCC) after receiving lenvatinib.
Main Methods:
- Retrospective analysis of International Metastatic RCC Database Consortium (IMDC) data.
- Patients were divided into second-line and third-line cohorts post-lenvatinib treatment.
- Primary endpoint was objective response rate (ORR); secondary endpoint was time to treatment failure (TTF).
Main Results:
- In the second-line cohort (n=20), ORR was 5% and median TTF was 5.8 months.
- In the third-line cohort (n=34), ORR was 12% and median TTF was 2.8 months.
- Most patients in the third-line cohort received everolimus + lenvatinib as second-line therapy.
Conclusions:
- TKI-based therapy demonstrates modest activity after lenvatinib exposure in mRCC patients.
- The findings underscore the need for improved treatment strategies for patients progressing on lenvatinib-based therapies.
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