Combination Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis

Area of Science:

• Oncology
• Clinical Pharmacology
• Medical Statistics

Background:

• Combination therapies for metastatic renal cell carcinoma (mRCC) show improved progression-free survival (PFS) over sunitinib monotherapy.
• Direct comparisons between different combination strategies are lacking, creating uncertainty regarding optimal treatment selection.
• Immune checkpoint inhibitors combined with axitinib or bevacizumab are key combination strategies in mRCC.

Purpose of the Study:

• To conduct a network meta-analysis comparing combination therapies for mRCC.
• To establish a rank order preference for combination strategies based on PFS and adverse events (AEs).
• To identify the preferred combination therapy for mRCC patients.

Main Methods:

• Systematic literature search for mRCC combination therapy studies up to July 2019.
• Inclusion of studies reporting immune checkpoint inhibitor plus axitinib or bevacizumab combinations.
• Application of a frequentist method for rank order generation of treatments.

Main Results:

• Three studies with 2672 patients were analyzed; all combinations improved PFS compared to sunitinib.
• Pembrolizumab plus axitinib demonstrated the highest probability of favorability for PFS (SUCRA 0.9).
• Pembrolizumab plus axitinib also showed the lowest incidence of Grade 3 or higher adverse events (SUCRA 0).

Conclusions:

• Combination of pembrolizumab plus axitinib is suggested as the preferred mRCC treatment option.
• This preference is based on superior efficacy (PFS) and a favorable safety profile (AEs).
• All evaluated combination strategies significantly improved PFS in mRCC patients compared to sunitinib.