Safety evaluation of immune-based combinations in patients with advanced renal cell carcinoma: a systematic review and meta-analysis

ABSTRACT

Introduction

Immune-based combinations, including nivolumab plus ipilimumab, pembrolizumab plus axitinib, and (at a lesser extent) avelumab plus axitinib, should be regarded among the new standards of care for first line therapy of metastatic renal cell carcinoma. Toxicity profiles are different among all these above combinations, as well as between them and targeted agents monotherapies, including sunitinib (i.e. the control arm of all the above studies).

Areas covered

We performed a systematic review and meta-analysis with the aim to compare adverse events from immune-based combinations versus sunitinib monotherapy across four recent randomized controlled trials (CheckMate-214, Keynote-426, IMmotion-151, and JAVELIN Renal 101) of front-line treatment for metastatic renal cell carcinoma, with particular attention to those from the ipilimumab plus nivolumab combination.

Expert opinion

Beyond efficacy and activity, the ipilimumab plus nivolumab combination appears feasible, being endowed by an acceptable safety profile, in line with that of the other available options for the treatment of metastatic RCC. The different patterns of toxicities emerging from this systematic review and meta-analysis need to be kept in mind while choosing the appropriate treatment for each individual patient. Furthermore, prevention, prompt identification, and treatment of immune-related adverse events remains an area to be improved.

KEYWORDS:

• Immune-checkpoint inhibitors
• kinase inhibitors
• combinations
• metastatic renal cell carcinoma
• systematic review
• meta-analysis

Article highlights

• We performed a systematic review and meta-analysis with the aim to compare adverse events from immune-based combinations versus sunitinib monotherapy, given as a front-line treatment for metastatic renal cell carcinoma patients.

• Particular attention was given to the safety profile of the ipilimumab plus nivolumab combination.

• As a whole, immune-based combinations seem not to be significantly more toxic when compared to sunitinib monotherapy when given according to its standard schedule.

• Beyond positively impacting on the OS of IMDC intermediate- and poor-risk patients, the ipilimumab plus nivolumab combination proved to be well tolerated with a predictable safety profile which tends to ameliorate over time, when nivolumab monotherapy is continued, after ipilimumab withdrawal.

• The different patterns of toxicities emerging from this systematic review and meta-analysis need to be kept in mind while choosing the appropriate treatment for each individual patient.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have worked with BMS, MSD, and Pfizer. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was not funded.