710P Phase II trial of lenvatinib (LEN) + pembrolizumab (PEMBRO) for progressive disease after PD-1/PD-L1 immune checkpoint inhibitor (ICI) in metastatic clear cell (mcc) renal cell carcinoma (RCC): Results by independent imaging review and subgroup analyses

Ch, Lee; Shah, Amishi Yogesh; Hsieh, James J.; Rao, Arpit; Pinto, Álvaro; Bilen, Mehmet Asım; Cohn, Allen Lee; Simone, Christopher Di; Shaffer, David R.; Sarrió, Regina Gironés; Ribe, Sara Gunnestad; Wu, Jane; Schmidt, Emmett V.; Kubiak, Peter; Okpara, Chinyere; Smith, Alan D.; Motzer, Robert J.

doi:10.1016/j.annonc.2020.08.782

Cited by 5 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The PFS were 11.7 and 11.3, respectively, and the ORR were 54.8% and 51.9%, respectively. However, all patients had already progressed on a prior line of therapy to a PD-(L)1 inhibitor, making the results hardly applicable in evaluating PP in the first-line setting [57].…”

Section: Pseudoprogressionmentioning

confidence: 99%

Navigating the ICI Combination Treatment Journey: Patterns of Response and Progression to First-Line ICI-Based Combination Treatment in Metastatic Renal Cell Carcinoma

Samuelly,

Di Stefano,

Turco

et al. 2024

JCM

View full text Add to dashboard Cite

The use of immune checkpoint inhibitors (ICIs) in combination with tyrosine kinase inhibitors or other ICIs has significantly improved the prognosis for patients with mccRCC. This marks a major milestone in the treatment of mccRCC. Nonetheless, most patients will discontinue first-line therapy. In this narrative review, we analyze the different patterns of treatment discontinuation in the four pivotal phase III trials that have shown an improvement in overall survival in mccRCC first-line therapy, starting from 1 January 2017 to 1 June 2023. We highlight the different discontinuation scenarios and their influences on subsequent treatment options, aiming to provide more data to clinicians to navigate a complex decision-making process through a narrative review approach. We have identified several causes for discontinuations for patients treated with ICI-based combinations, such as interruption for drug-related adverse events, ICI treatment completion, treatment discontinuation due to complete response or maximum clinical benefit, or due to progression (pseudoprogression, systemic progression, and oligoprogression); for each case, an extensive analysis of the trials and current medical review has been conducted.

show abstract

Section: Pseudoprogressionmentioning

confidence: 99%

Navigating the ICI Combination Treatment Journey: Patterns of Response and Progression to First-Line ICI-Based Combination Treatment in Metastatic Renal Cell Carcinoma

Samuelly,

Di Stefano,

Turco

et al. 2024

JCM

View full text Add to dashboard Cite

show abstract

“…A phase II trial of lenvatinib plus pembrolizumab in 104 mRCC patients that were not responding to treatment with immunotherapy was also presented[ 24 ]. The ORR was 51%, PFS 11.7 mo, and mDOR 12.2 mo.…”

Section: Updates In American Society Of Clinical Oncology Genitourina...mentioning

confidence: 99%

Update on the treatment of metastatic renal cell carcinoma

López¹,

Belenchón²,

Mazuecos-Quirós³

et al. 2022

WJCO

View full text Add to dashboard Cite

Metastatic renal cell cancer (mRCC) management has undergone a paradigm shift in recent decades. The first revolution came with the emergence of vascular endothelial growth factor inhibitors; there was a second wave with the unprecedented success of checkpoint inhibitors, and then the latest approach, which is becoming the new care standard in mRCC, of combining these two strategies in different ways. Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival (PFS), overall survival (OS), and objective response rate (ORR) in intermediate and high-risk patients. However, several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place, and so far, the only one for nivolumab/ipilimumab is the frontline setting. The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembroli-zumab/axitinib over sunitinib in favorable-risk mRCC, suggesting that it should no longer be the first line of choice in low-risk patients. Finally, the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS, OS, and ORR, providing a new first-line option among all International Metastatic RCC Database Consortium risk patients. Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib, cabozantinib/atezolizumab, and lenvatinib/pembrolizumab, providing promising grounds upon which to start phase III studies. In addition, other works are using novel therapeutic agents with different mechanisms of action, including telaglenastat (a glutaminase inhibitor), entinostat [an inhibitor of histone deacetylases (HDACs)], and olaparib and talazoparib, poly(ADP-ribose) polymerase inhibitors widely used in other tumors. However, some questions regarding mRCC management still need to be addressed, such as head-to-head comparisons between the current options, treatment sequencing, non-clear cell mRCC, and the role of biomarkers to ascertain the best treatment choice.

show abstract

“…Furthermore, lenvanib/pembrolizumab combination therapy has been evaluated in patients progressing on ICI therapy in a phase 2 trial [52 ▪▪ ]. Lee et al evaluated the outcomes of 104 patients, most of whom had been previously treated with an ICI and a VEGF pathway-targeted agent (in combination or sequentially) (65%) or dual ICI (37%).…”

Section: Evidence Synthesismentioning

confidence: 99%

What is next in second- and later-line treatment of metastatic renal cell carcinoma? review of the recent literature

Mori

Schmidinger

Quhal

et al. 2021

Current Opinion in Urology

View full text Add to dashboard Cite

Purpose of reviewThe current treatment landscape of metastatic renal cell carcinoma has changed dramatically from the dominance of single-agent tyrosine kinase inhibitor (TKI) therapy to immune-checkpoint inhibitor (ICI)-based combinations in recent years. However, the optimal subsequent therapy remains ill-defined owing to the novelty of this approach. Recent findingsTreatment with TKIs after failure of single or dual ICI therapies may result in robust clinical efficacy. Nonetheless, there is a trend toward lower efficacy of TKIs after previous ICI-TKI combination therapy. Currently, tivozanib is the only drug whose third-and later-line use after failure of TKI and ICI is supported by evidence, with significantly longer progression-free survival and higher objective response rates than sorafenib. Data from retrospective studies highlight the safety and clinical activity of ICI rechallenge. SummaryOverall, the level of evidence remains low. Treatment after failure of dual ICI therapy is not well defined and may consist of any available TKI. Although first-line use of TKI is less common, strong evidence suggests cabozantinib or nivolumab as standard options in that setting. The recommendations after first-line TKI-ICI therapy failure mirror this recommendation, although the data are less robust. Keywords immune-checkpoint inhibitors, metastatic renal cell carcinoma, second-line treatment, tyrosine kinase inhibitors ]. In recent clinical trials, ICI-based combination therapies have markedly improved survival outcomes in mRCC patients compared with the previous standard of care (sunitinib) in first-line setting [5-8,9 && ].In an era of targeted therapy with antiangiogenic tyrosine kinase inhibitors (TKIs) for mRCC, approximately 52% and 35% of patients reach second-and third-line treatment, respectively [10].

show abstract

710P Phase II trial of lenvatinib (LEN) + pembrolizumab (PEMBRO) for progressive disease after PD-1/PD-L1 immune checkpoint inhibitor (ICI) in metastatic clear cell (mcc) renal cell carcinoma (RCC): Results by independent imaging review and subgroup analyses

Cited by 5 publications

References 0 publications

Navigating the ICI Combination Treatment Journey: Patterns of Response and Progression to First-Line ICI-Based Combination Treatment in Metastatic Renal Cell Carcinoma

Navigating the ICI Combination Treatment Journey: Patterns of Response and Progression to First-Line ICI-Based Combination Treatment in Metastatic Renal Cell Carcinoma

Update on the treatment of metastatic renal cell carcinoma

What is next in second- and later-line treatment of metastatic renal cell carcinoma? review of the recent literature

Contact Info

Product

Resources

About