Conditional immune adverse event rate in urothelial and renal cell carcinoma patients treated with immune checkpoint inhibitors.

Authors

Pier VItale Nuzzo

Pier Vitale Nuzzo

DFCI, Brookline, MA

Pier Vitale Nuzzo , Gregory Russell Pond , Sarah Abou Alaiwi , Amin Nassar , Ronan Flippot , Catherine Curran , Kerry L. Kilbridge , Xiao X. Wei , Bradley Alexander McGregor , Lauren Christine Harshman , Toni K. Choueiri , Guru Sonpavde

Organizations

DFCI, Brookline, MA, McMaster University, Department of Oncology, Hamilton, ON, Canada, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, Brigham and Women's Hospital, Boston, MA, Laboratory of Avec Foundation, Hopital Piti-Salpetriere, Paris, France, Dana Farber Cancer Institute, Boston, MA, Lank Center for Genitourinary Malignancy, Dana-Farber Cancer Institute, Boston, MA, Dana-Farber Cancer Institute, Boston, MA, Stanford University School of Medicine, Stanford, CA, Dana-Farber Cancer Institute/Brigham and Women’s Hospital and Harvard University School of Medicine, Boston, MA

Research Funding

No funding received
None.

Background: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). While the incidence and prevalence of irAEs have been well characterized in the literature, much less is known about the cumulative incidence (CI) rate of irAEs. We sought to evaluate the CI of irAEs in metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC) patients (pts) treated with ICIs. Methods: We identified a cohort of mUC and mRCC pts who received ICIs at DFCI. irAEs were classified using CTCAE v.5.0 guidelines. The CI rate was a defined measure that accounted for elapsed time since treatment initiation and estimated the risk of irAE development conditioned on time elapsed without experiencing an irAE, accounting for the competing risk of death. Incidence and CI of irAEs at each monthly landmark time was calculated. Prognostic factors of irAE were assessed using the Fine and Gray method. Results: A total of 470 pts was treated with ICIs between July 2013 and October 2018 [mUC: 199 (42.3%); mRCC: 271 (57.7%)]. 341 (72.6%) pts received ICI monotherapy, 86 (18.3%) received ICIs in combination with targeted therapies, and 43 (9.2%) received a combination of two ICIs. Overall, 186 pts (39.5%) experienced any irAE at any time point. Common irAEs included hypothyroidism (n=42 [22.6%]), skin (n=36 [19.4%]), colitis (n=35 [18.8%]), transaminitis (n=32 [17.2%]), and pneumonitis (n=14 [7.5%]). The risk of developing an irAE over time was as follows: 33.5% if no irAE within the 1st month(mo), 27.3% if no irAE in 3mo, 18.8% if no irAE in 6mo, and 16.4% if no irAE by 12mo. No difference was observed in CI based on type of cancer (mUC vs mRCC) or agent (PD1 vs. PD-L1). Multivariable analysis showed that ICI combined with ICI or other agents vs. ICI monotherapy (p<0.001), firstline therapy (p=0.013) and PD-1 vs. PD-L1 inhibitors (p=0.008) were statistically correlated with the development of irAEs. Conclusions: This study quantitates the incidence of developing irAEs with ICI conditioned on time elapsed without irAE development. Although the incidence of irAEs decreased over time on therapy, irAEs require continuous vigilant monitoring because of the long tail in its incidence.

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Abstract Details

Meeting

2020 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Prostate Cancer; Urothelial Carcinoma; Penile, Urethral, Testicular, and Adrenal Cancers

Track

Urothelial Carcinoma,Adrenal Cancer,Penile Cancer,Prostate Cancer - Advanced,Prostate Cancer - Localized,Testicular Cancer,Urethral Cancer

Sub Track

Symptoms, Toxicities, and Whole-Person Care

Citation

J Clin Oncol 38, 2020 (suppl 6; abstr 481)

Abstract #

481

Poster Bd #

H4

Abstract Disclosures

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