Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not

Otto Hemminki; Nathan Perlis; Johan Bjorklund; Antonio Finelli; Alexandre R Zlotta; Akseli Hemminki

doi:10.1016/j.euros.2020.11.003

Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not

Eur Urol Open Sci. 2020 Nov 28:22:61-73. doi: 10.1016/j.euros.2020.11.003. eCollection 2020 Dec.

Authors

Otto Hemminki^{1

2

3}, Nathan Perlis¹, Johan Bjorklund^{1

4}, Antonio Finelli¹, Alexandre R Zlotta¹, Akseli Hemminki^{3

5}

Affiliations

¹ Division of Urologic Oncology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada.
² Helsinki University Hospital, Department of Urology, Helsinki, Finland.
³ Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.
⁴ Institution for Molecular Medicine and Surgery, Urology, Karolinska Institutet, Stockholm, Sweden.
⁵ Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.

Abstract

Context: Current guidelines suggest several targeted therapies (TTs) and immunotherapies (ITs) in the treatment of advanced or metastatic renal cell carcinoma (mRCC). Ideal sequencing of these treatments is unclear.

Objective: The primary objective was to evaluate the overall survival (OS) data of the treatments approved for mRCC. Secondary objectives included evaluating other signs of efficacy and adverse events.

Evidence acquisition: We reviewed the current Food and Drug Administration-approved treatments for mRCC. Trials associated with approval were reviewed. We also included pre- and postapproval publications when appropriate.

Evidence synthesis: There is minimal evidence supporting OS benefit for the nine approved TTs. They result in adverse events and are a considerable economic burden. For these reasons, their future role in mRCC treatment should be re-evaluated, given the emergence of IT that have demonstrated OS benefits. Accumulating long-term survival data with high-dose interleukin-2 treatment suggests that this older treatment could still be considered for eligible patients. Checkpoint inhibitors have shown promising OS and durable responses; as such, the high cost of treatment might be justified. However, the available evidence does not suggest that adding TT to IT would increase efficacy over IT alone, but would add toxicity.

Conclusions: Trial data supporting OS benefit are much stronger for ITs than for TTs. Combining checkpoint inhibitors with TTs has not been shown to produce better OS than checkpoint inhibitors alone, while more adverse events are present. Granting drug approvals based on efficacy without demonstrated OS benefit should be revisited.

Patient summary: Approved treatments for metastatic kidney cancer include targeted and immune-based therapies. The former commonly produces temporary tumour shrinkage, but survival benefits are unclear. All approved immunotherapies have increased survival, and a proportion of patients appear cured.

Keywords: Advanced; Advanced renal cell carcinoma; Approved; Kidney cancer; Metastatic; Metastatic renal cell carcinoma; Quality of life; Renal cell carcinoma; Review; Survival; Treatments.

Publication types

Review