Adjuvant immunotherapy for locally advanced renal cell carcinoma

ABSTRACT

Introduction

Locally advanced renal cell carcinoma (RCC) presents a therapeutic challenge due to 20–40% relapse risk post-nephrectomy. There has been substantial interest in utilizing immunotherapy interrupting the PD-1/PD-L1 axis in the perioperative space, especially in the adjuvant setting, in order to minimize such risk.

Areas covered

We conducted a PubMed search using the terms ‘adjuvant’ and ‘RCC.’ We begin by examining landmark studies in the postoperative space for locally advanced RCC, with special emphasis on immunotherapeutic biologics. Important considerations are outlined in an effort to explain the conflicting data on the benefit of adjuvant immunotherapy as well as to adequately assess the magnitude of potential benefit of the recently approved adjuvant pembrolizumab. Relevant contemporary challenges and opportunities as well as future directions of the field are also discussed.

Expert opinion

Systemic immunotherapy with monoclonal antibodies targeting the PD-1/PD-L1 axis likely holds promise, either alone or potentially in combinations, in minimizing recurrence risk for locally advanced RCC. However, emphasis on post-protocol care, robust endpoint selection, and continued work and validation on predictive biomarkers are needed to confidently select those patients that may benefit the most and minimize biologic and financial toxicity.

KEYWORDS:

• Adjuvant
• immunotherapy
• kidney
• cancer
• review
• RCC

Article highlights

• Locally advanced RCC has a considerable risk of recurrence after nephrectomy. Prior attempts to utilize adjuvant VEGF-targeting TKIs and prior therapeutics were largely unsuccessful in improving outcomes.

• The success of immunotherapy targeting the PD-1/PD-L1 axis in advanced RCC led to studies exploring their use in the perioperative space.

• The results of such studies have been mixed, with DFS improvement noted with adjuvant pembrolizumab but no benefit with adjuvant atezolizumab, adjuvant nivolumab and ipilimumab, and perioperative nivolumab.

• These differences can be potentially attributed to differences in drug efficacy and patient selection. Scrutiny of post-protocol care is required to accurately assess the benefit of pembrolizumab in improving outcomes.

• Future studies should focus on predictive biomarkers, identification of patient groups most likely to benefit, and novel therapeutic combinations.

Declaration of interest

D McDermott reports consulting honoraria from BMS, Pfizer, Merck, Eisai Inc, Xilio, Aveo, Genentech, Cullinan, Exelixis, and cancer research support from BMS, Merck, Genentech, Pfizer, Exelixis, X4 Pharma, Alkermes Inc. 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

A reviewer on this manuscript has disclosed being on the advisory board for BMS, MSD, Ipsen, EISIA, and Pfizer. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.