BPI20-013: A Systematic Review and Meta-Analysis on Mucocutaneous Toxicities Associated With Upfront Use of Immune Checkpoint Inhibitor and Anti-Angiogenic Tyrosine Kinase Inhibitor Combinations for Advanced Renal Cell Carcinoma

Background: In recent clinical trials, immune checkpoint inhibitor (ICI) and anti-angiogenic tyrosine kinase inhibitor (VEGFi) combinations have shown superior outcomes compared to the previous standard of care sunitinib as the first-line treatment for advanced renal cell carcinoma (aRCC). When used individually, both ICIs and VEGFis have significant mucocutaneous toxicities. We performed a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of different mucocutaneous toxicities associated with ICI and VEGFi combinations in first-line treatment of aRCC. Methods: We conducted a systematic search in PUBMED, MEDLINE, EMBASE, and meeting Abstracts as per PRISMA guidelines from inception until May 2019. We included phase 3 RCTs using ICI and VEGFi combinations in the intervention arm for the first-line treatment of aRCC. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2-value. Results: Two RCTs, JAVELIN Renal 101 and KEYNOTE-426, randomizing 1727 patients (863 in the intervention arms and 864 in the control arms) were included in the final analysis. JAVELIN Renal 101 used avelumab and axitinib and KEYNOTE-426 used pembrolizumab and axitinib combination in the intervention arms, while sunitinib was used in the control arms for both studies. The randomization was 1:1 in both studies. The pooled RR of any-grade mucocutaneous toxicities are as follows — palmar-plantar erythrodysesthesia (PPE): 0.83 (95% CI: 0.59-1.17, P = 0.29, I2 = 85%); rash: 1.28 (95% CI: 1.00-1.65, P = 0.05, I2 = 0%); pruritus: 2.68 (95% CI: 1.94-3.70, P < 0.00001, I2 = 0%); and stomatitis: 0.87 (95% CI: 0.65-1.17, P = 0.36, I2 = 58%). The pooled RR of grade 3 and higher mucocutaneous toxicities are as follows — PPE: 1.35 (95% CI: 0.88-2.06, P = 0.17, I2 = 0% ); rash: 0.76 (95% CI: 0.17-3.46, P = 0.72, I2 = 0%); stomatitis: 0.83 (95% CI: 0.14-4.93, P = 0.84, I2 = 75%). Conclusions: ICI and VEGFi combinations are associated with increased risk of any-grade pruritus and rash compared to sunitinib. However, two more serious mucocutaneous toxicities, PPE and stomatitis, were not significantly different between ICI and VEGFi combination arms and sunitinib arms.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Corresponding Author: Nusrat Jahan, MD
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 33 33 33
PDF Downloads 118 118 118
EPUB Downloads 0 0 0