Incidence and risk of colitis with programmed death-1 versus programmed death-ligand 1 inhibitors for the treatment of cancer.

Authors

Hirotaka Miyashita

Hirotaka Miyashita

Mount Sinai Beth Israel, New York, NY

Hirotaka Miyashita , Takahisa Mikami , Sera Satoi , Christina Cruz , Matt D. Galsky

Organizations

Mount Sinai Beth Israel, New York, NY, Nippon Medical School Hospital, Tokyo, Japan, Mount Sinai Hospital, New York, NY

Research Funding

No funding received
None

Background: Programmed death 1 (PD-1) inhibitors and Programmed Death-Ligand 1 (PD-L1) inhibitors are immune checkpoint inhibitors (ICIs) approved for treatment of several different cancers. Colitis is a major immune-related adverse event associated with ICIs, but the risk of colitis with PD-1 versus PD-L1 inhibitors is not well characterized. Methods: We performed a meta-analysis for the incidence of all grade and grade 3-4 colitis with PD-1 inhibitor (nivolumab, pembrolizumab, and cemiplimab) or PD-L1 inhibitor (atezolizumab, avelumab, and durvalumab) monotherapy using a fixed effects model. We also conducted subgroup meta-analyses of non-small cell lung cancer (NSCLC) or urothelial carcinoma (UC) trials, and a network meta-analysis of randomized trials comparing PD-1 or PD-L1 inhibitors with docetaxel for NSCLC. We analyzed Food and Drug Administration Adverse Event Reporting System (FAERS) database to estimate the reporting odds ratio (ROR) of each medication, which provides the estimated relative risk most valid in spontaneous report database. Results: We identified 88 studies that met inclusion for the analysis. PD-1 inhibitors were associated with higher incidence of all grade and grade 3-4 colitis compared to PD-L1 inhibitors in the analysis of all cancer types (1.49% vs 0.83%, relative risk (RR); 1.80, 95% confidence interval (CI); 1.22-2.67 for all grade colitis, and 0.85% vs 0.34%, RR; 2.52, 95% CI; 1.46-4.37 for grade 3-4 colitis). The meta-analyses on NSCLC and UC, and the network meta-analysis on NSCLC also showed the tendency that PD-1 inhibitors are associated with higher risk of all grade and grade 3-4 colitis, though only the analysis on UC for all grade colitis showed a significant difference. (1.95% vs 0.64%, RR; 3.05, 95% CI; 1.18 - 7.88) Retrospective analysis showed ROR of 16.78 (95% CI; 15.8-17.8) for PD-1 inhibitors, and 12.93 (95% CI; 10.74-15.42) for PD-L1 inhibitors. We found that ROR of PD-1inhibitors was 1.17 (95% CI; 0.97-1.43) compared to PD-L1 inhibitors. Conclusions: Our study showed that PD-1 inhibitors have higher risk of colitis than PD-L1 inhibitors.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Publication Only

Session Title

Publication Only: Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics—Immunotherapy

Sub Track

Immune Checkpoint Inhibitors

Citation

J Clin Oncol 38: 2020 (suppl; abstr e15087)

DOI

10.1200/JCO.2020.38.15_suppl.e15087

Abstract #

e15087

Abstract Disclosures

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