Phase II study of lenvatinib plus pembrolizumab for disease progression after PD-1/PD-L1 immune checkpoint inhibitor in metastatic clear cell renal cell carcinoma (mccRCC): Results of an interim analysis

Lee, C.-H.; Shah, Amishi Yogesh; Makker, Vicky; Taylor, Matthew H.; Shaffer, David R.; Hsieh, James J.; Cohn, Allen Lee; DiSimone, Christopher; Marín, Álvaro Pinto; Rasco, Drew W.; Ribe, Sara Gunnestad; Richards, Donald A.; Stepan, Daniel E.; Dutcus, Corina E.; Wu, Jane; Schmidt, Emmett V.; Perini, Rodolfo F.; Motzer, Robert J.

doi:10.1093/annonc/mdz253.013

Cited by 4 publications

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“…Axitinib treatment was associated with high clinical activity (45% ORR with 67% of responses lasting > 12 months and a PFS of 8.8 months). Lee et al recently reported interim analysis of a phase 2 multicentre study which examined the question of salvage therapy with IO based combination after prior IO failure [25] (NCT02501096). In this study, 33 patients who progressed on IO treatment received pembrolizumab and lenvatinib combination, which was associated with promising results in this setting with ORR of 64% and 11.3 months PFS indicating that salvage therapy after IO failure with a combination of IO and VEGF targeted therapy is a feasible approach.…”

Section: Discussionmentioning

confidence: 99%

Systemic therapy for advanced clear cell renal cell carcinoma after discontinuation of immune-oncology and VEGF targeted therapy combinations

Ged

Gupta

Düzgöl³

et al. 2020

BMC Urol

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Background: Several phase 3 studies reported positive results for combinations of Immune-Oncology (IO) and Vascular Endothelial Growth Factor (VEGF) targeted therapies in patients with metastatic clear cell Renal Cell Carcinoma (ccRCC). However, there are limited data on outcomes to systemic therapy after IO-VEGF combinations. Methods: A retrospective analysis was performed on patients with metastatic ccRCC treated at the Memorial Sloan Kettering Cancer Center and Cleveland Clinic who initiated systemic therapy post IO-VEGF including combinations with VEGF receptor (VEGFR) tyrosine kinase inhibitors (IO-TKI) and combinations with the anti-VEGF monoclonal antibody bevacizumab (IO-Bev). The study objectives were to evaluate the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) on systemic therapy post IO-VEGF. RECIST v1.1 criteria were used to determine radiological responses and progression. Survival estimates were evaluated with the Kaplan-Meier methods and the log-rank test from the start of systemic therapy post IO-VEGF to the event of interest. Results: A total of fifty-nine patients were treated post discontinuation of IO-VEGF regimens which included IO-Bev (n = 35; 59%) and IO-TKI (n = 24; 41%). Fifty-eight patients (98%) received IO-VEGF regimens as part of a clinical trial. Subsequent therapies included cabozantinib (n = 22; 37%), axitinib (n = 18; 31%), pazopanib (n = 4; 7%), lenvatinib and everolimus (n = 4; 7%), mTOR inhibitor monotherapy (n = 3; 5%), axitinib and dalantercept (n = 2; 3%), sunitinib (n = 1; 2%), sorafenib (n = 1; 2%), and treatment with agents on unreported clinical trials (n = 4; 7%). Patients treated on unreported clinical trials were excluded from the efficacy analysis. Post IO-VEGF, the ORR was 25% and median PFS was 12.0 months (95% CI, 8.2-24.5). Median OS was 24.5 months (95% CI, 12-NE) and 12 months OS rate was 63.3% (95% CI, 48.6-74.9). We observed no differences post IO-VEGF OS when comparing IO-TKI vs IO-Bev (Log-rank p = 0.73). Conclusions: Post IO-VEGF, most patients received VEGFR-TKIs. In this setting, VEGFR-TKIs demonstrated clinical activity and remain a viable option for salvage therapy after progression on IO-VEGF.

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Section: Discussionmentioning

confidence: 99%

Systemic therapy for advanced clear cell renal cell carcinoma after discontinuation of immune-oncology and VEGF targeted therapy combinations

Ged

Gupta

Düzgöl³

et al. 2020

BMC Urol

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“…Besides, several ongoing trials are focused on the efficacy and safety of immune-based treatment in the second-line setting. In the 2019 ESMO meeting, Lee et al [ 28 ] reported the results of the phase II clinical trial of lenvatinib plus pembrolizumab treating mRCC patients who progressed from prior immune checkpoint therapy. With ≥12 of follow-up for 33 patients enrolled, the ORR was 52%, and DCR was 94%, which demonstrated promising antitumor activity of lenvatinib and pembrolizumab combined treatment.…”

Section: Discussionmentioning

confidence: 99%

Systemic therapies for metastatic renal cell carcinoma in the second-line setting: A systematic review and network meta-analysis

Liao¹,

Hou²,

Han³

et al. 2022

Medicine

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Objectives: To perform a systematic review and network meta-analysis to compare the survival benefit and safety profile of current available second-line treatment options of metastatic renal cell carcinomav. Methods: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically researched for eligible articles which were published before July 20, 2021. Studies comparing overall/progression free survival (OS/PFS), objective response rate (ORR), and/or adverse events (AEs) in patients with metastatic renal cell carcinomav were included. Results: Nine trials (with 4911 patients) were finally included for final network meta-analysis. Cabozantinib, lenvatinib, and lenvatinib plus everolimus were associated with significantly better PFS, OS, and ORR compared with everolimus, and lenvatinib plus everolimus emerged as the best option. As for grade 3 to 4 AEs, nivolumab showed significantly lower risk of AEs compared with everolimus. Other included treatments were associated with significantly increased risk of AEs. When comprehensively assessed the efficacy and safety of included treatments based on the ranking analysis of PFS, ORR, and grade 3 to 4 AEs, lenvatinib plus everolimus, cabozantinib, and nivolumab showed superior efficacy over other treatments, with relatively lower risk of grade 3 to 4 AEs. Conclusions: Among all included therapies, Lenvatinib plus everolimus was identified as the most effective treatment approach, with the best PFS, OS, and ORR. nivolumab was associated with decreased incidence of grade 3 to 4 AEs among included treatment therapies. When comprehensively evaluated the efficacy and safety of included treatment options, lenvatinib plus everolimus, cabozantinb, and nivolumab were associated with better survival benefits and lower risk of AEs. Future studies should focus on the direct comparison of different second-line treatment in real-world populations.

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“…Emerging data from prospective studies and real world data have begun to explore the role of IO combination therapy in the subsequent treatment setting. In a phase II clinical trial, lenvatinib plus pembrolizumab produced a median PFS of 11.7 months as second-or third-line treatment after progression on a PD-1 or PD-L1 agent [44]. Our group has also found that sitravatinib plus nivolumab has significant activity after progression on TKI, and the combination is now being studied after progression on PD-1 or PD-L1 therapies [45].…”

Section: Impact On First Line Treatment Decision On Subsequent Therapymentioning

confidence: 94%

First-Line Immuno-Oncology Combinations for Metastatic Clear Cell Renal Cell Carcinoma (mRCC): A Systematic Review of Phase III Clinical Trials

Hahn

Shah

Campbell

2021

KCA

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BACKGROUND: The introduction of immune checkpoint inhibitors rapidly changed treatment for patients with metastatic clear cell renal cell carcinoma (mRCC). First-line treatment now includes multiple immuno-oncology (IO) combinations that were approved over a short time period and were not directly compared in randomized clinical trials. Thus, clinicians face a challenge in individualizing first-line treatment to optimize clinical outcomes. OBJECTIVE: We sought to systematically review clinical outcomes for first-line IO combinations for patients with mRCC. METHODS: Literature reporting outcomes from phase III clinical trials that evaluated first-line IO combination therapies was identified through a search of the PubMed electronic database following PRISMA guidelines. Abstracts were screened to identify manuscripts that fit the search criteria, and then, a descriptive review was performed. RESULTS: Our literature search identified 2,229 abstracts that met the initial search criteria, and then, it was narrowed to 431 abstracts using filters for “clinical trial” and a “ten year” time window. After review of the abstracts, six manuscripts were selected for data extraction and subsequent review. CONCLUSION: When compared to sunitinib, four IO combinations improved overall survival as first-line treatment, and five improved progression free survival for patients with mRCC. These IO combination therapies have unique characteristics, so clinicians should take into account patient and cancer factors to individualize treatment recommendations.

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Phase II study of lenvatinib plus pembrolizumab for disease progression after PD-1/PD-L1 immune checkpoint inhibitor in metastatic clear cell renal cell carcinoma (mccRCC): Results of an interim analysis

Cited by 4 publications

References 0 publications

Systemic therapy for advanced clear cell renal cell carcinoma after discontinuation of immune-oncology and VEGF targeted therapy combinations

Systemic therapy for advanced clear cell renal cell carcinoma after discontinuation of immune-oncology and VEGF targeted therapy combinations

Systemic therapies for metastatic renal cell carcinoma in the second-line setting: A systematic review and network meta-analysis

First-Line Immuno-Oncology Combinations for Metastatic Clear Cell Renal Cell Carcinoma (mRCC): A Systematic Review of Phase III Clinical Trials

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