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

Abstract

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].

Application of the Meet-URO score to metastatic renal cell carcinoma patients treated with second- and third-line cabozantinib

“…Over the past 5 years, an increasing number of novel drugs and immunotherapy-based combinations have been approved for the treatment of mRCC. 12 , 13 In addition to improved activity, these therapies have different pharmacokinetic characteristics and mechanisms of action compared to the pre-existing targeted therapies (e.g. sunitinib, sorafenib, pazopanib and axitinib), which were the treatments available at the time the IMDC prognostic classification was developed.…”

Outcomes of axitinib versus sunitinib as first‐line therapy to patients with metastatic renal cell carcinoma in the immune‐oncology era

“…23 These patients need second-or later-line therapy, and VEGFR-TKIs are the main options in these situations. 9 Although the National Comprehensive Cancer Network guidelines recommend four VEGFR-TKIs as category 1 drugs, 24 it is not known which drug is preferable as sequential therapy. In the last 5 years, cabozantinib has been considered the main second-line therapy after IO drugs, especially after IO plus axitinib therapy.…”

“…In this regard, VEGFR-TKIs are thought to be the mainstay treatments, while IO drugs remain the standard treatment. 9 This study was aimed at comparing the clinical efficacy of axitinib and sunitinib used in Japanese patients with mRCC for elucidating an optimal VEGFR-TKI in the IO era.…”

Aktuelles zur medikamentösen Therapie des rezidivierten/metastasierten Nierenzellkarzinom (mNCC)

“…Vergleichende Phase III Daten zur Sicherheit und Effektivität der potentiell einsetzbaren Substanzen nach erfolgter Vorbehandlung mit Checkpointinhibitoren sind bisher nicht erhoben worden. Die aktuelle Evidenzlage für die Zweitlinie und für jedwede post-CPI Behandlung des mNCCS erfolgt auf dem Boden der Ergebnisse aus nicht-kontrollierten, prospektiven Studien, Subgruppenanalysen prospektiver randomisierter Studien sowie retrospektiver Analysen [15,16].…”