Immune checkpoint inhibition for the treatment of renal cell carcinoma

ABSTRACT

Introduction: The systemic therapy in metastatic renal cell carcinoma (mRCC) is moving from tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors to immune checkpoint inhibitors and its combination with TKIs.

Areas covered: This review provides a general overview using immune checkpoint inhibition for the treatment of RCC. Clinical results from conducted and ongoing clinical trials are summarized and checkpoint inhibition is reviewed in the context to other available systemic therapies such as TKIs for mRCC based on the different International Metastastic RCC Database Consortium (IMCD) risk groups. Furthermore, prospects for the use of predictive biomarkers in the decision-making process of chosen therapy will be given.

Expert opinion: Using checkpoint inhibition in mRCC has demonstrated a superior efficacy for patients with IMDC intermediate and poor risk for ipilimumab combined with nivolumab. Furthermore, therapeutic regimes with tyrosine kinase inhibition plus immune checkpoint-inhibition were recently presented and demonstrated superiority in all risk groups for axitinib plus pembrolizumab in overall survival and progression-free survival (PFS) and axitinib plus avelumab in PFS compared to sunitinib monotherapy. Novel biomarkers of response to further optimize therapeutic selection and patient outcomes are ongoing medical objectives.

KEYWORDS:

• Biomarker
• checkpoint inhibition
• CTLA-4
• PD-1
• PD-L1
• renal cell carcinoma

Article Highlights

• Immune checkpoint inhibitors such as PD-1 inhibitors have enriched the treatment landscape of mRCC patients in the second- and first-line treatment.

• Recent data indicate that the combination of the immune checkpoint inhibitors nivolumab (PD-1) and ipilimumab (CTLA-4) is superior to TKI treatment in the IMDC intermediate and poor prognosis group of mRCC patients.

• The combination of the PD-1 inhibitor pembrolizumab or the PD-L1 inhibitor avelumab to the TKI axitinib significantly prolongs PFS and OS (pembrolizumab) or PFS (avelumab) when compared to TKI monotherapy in all comers.

• A distinctive biomarker to forecast prognosis and response to immune checkpoint inhibition in mRCC is still missing.

• Adjuvant trials of immune checkpoint inhibitors in ccRCC are still ongoing.

This box summarizes key points contained in the article.

Declaration of interest

J Bedke reports consultancies and speaker´s Bureau: BMS; Eisai, EUSA, Ipsen, Novartis, MSD, Pfizer, Roche and study participation with institutional funding: Bayer, BMS; Eisai, Ipsen, Novartis, MSD, Pfizer, Roche, Exelixis. A Stenzl reports consultancies and speaker´s Bureau: Ipsen, Roche, Janssen, BMS, Alere, Stebabiotech, Synergo, Ferring, Astellas, Amgen, Sanofi Aventis, CureVac and study participation or research grants with institutional funding: Johnson & Johnson, Roche, Cepheid, Amgen, Bayer, CureVac, GemeDx biotechnologies GmbH, Novartis, Karl Storz, immatics biotechnologies GmbH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One of the reviewers on this manuscript has received consulting and research funding from BMS, Pfizer, Merck, and Roche. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.