715P - Immune checkpoint therapy (ICT) re-challenge after immune-related adverse events (irAEs) in genitourinary cancers (GUC)

Background

ICT prolongs survival in subsets of cancer patients (pts) and can trigger irAEs. Previous studies of ICT re-challenge after irAEs have been limited to one cancer type or focused only on recurrence rates. We analyzed safety and efficacy after ICT re-challenge across GUC.

Methods

This study was conducted under an IRB-approved protocol. Medical records of pts with prostate cancer (PCa), renal cell carcinoma (RCC), and urothelial carcinoma (UC) at our institution (9/25/13-11/1/19) who received ICT and had irAEs were reviewed. Demographic, safety, and outcomes data (RECIST or irRECIST) were collected.

Results

Of 30,681 records queried, 1,141 met search criteria. 390 pts (PCa, n=104; RCC, n=166; UC, n=120) who received ICT (Table) and had irAEs were identified. 524 irAEs (G1:130, G2:196, G3:177, G4:15, G5: 6) were identified, including colitis (n=90), thyroiditis (n=84), hepatitis (n=42), and pneumonitis (n=40). Pts received corticosteroids (n=241), infliximab (n=36), vedolizumab (n=18), tocilizumab (n=9), and secukinumab (n=1). ICT was held after irAE in 233/390 pts (60%) for median 28 days (IQR 15-38) and discontinued in 169/233 (73%). 64/233 pts (27%), who had irAEs including colitis (n=17, G1:2, G2:5, G3:10), pneumonitis (n=3, G:2), arthritis (n=6, G2:5, G3:1), were re-challenged. 20/64 pts (31%) had subsequent irAEs, including G4 myositis, G3 hepatitis, pancreatitis, colitis, and pneumonitis. 8/20 (40%) had new G3/4 irAEs and 5/20 (25%) had recrudescence of the same irAE, but no irAE-associated deaths. 9/64 (14%) pts with SD prior to re-challenge achieved PR (n=7) or CR (n=2) (Table). Targeted immunosuppression enabled ICT re-challenge in 9 cases (secukinumab for G2 psoriatic arthritis, vedolizumab [n=3] and infliximab [n=2] for G3 colitis, tocilizumab for G2/3 arthritis [n=3]). Table: 715P

Conclusions

In this retrospective analysis, 14% of pts achieved CR/PR from SD after ICT re-challenge. Targeted immunosuppression may permit ICT resumption in select cases.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S.K. Subudhi: Advisory/Consultancy: Amgen; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Apricity; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Cancer Now; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Dava Oncology; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Dendreon; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Janssen Oncology; Advisory/Consultancy: MEDACorp; Advisory/Consultancy: Polaris; Honoraria (self), Travel/Accommodation/Expenses: Parker Institute of Cancer Immunotherapy; Honoraria (self), Travel/Accommodation/Expenses: Society for the Immunotherapy of Cancer. J. Gao: Advisory/Consultancy: Symphogen; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Jounce; Advisory/Consultancy: Janssen; Research grant/Funding (self): Doris Duke Charitable Foundation. M.T. Campbell: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): EMD Serono; Non-remunerated activity/ies, Education Programs non-CME: Roche; Research grant/Funding (institution): ApricityHealth. A.Y. Shah: Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): EMD Serono; Honoraria (self): Pfizer; Honoraria (self): Oncology Information Group. P. Msaouel: Honoraria (self): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Mirati; Honoraria (self): Exelixis; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Gateway for Cancer Research. A.J. Zurita-Saavedra: Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy: Incyte; Advisory/Consultancy: Biocept; Research grant/Funding (institution): Infinity Pharma; Honoraria (self): McKesson Specialty Health; Honoraria (self): Janssen-Cliag. E. Jonasch: Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis. A.O. Siefker-Radtke: Advisory/Consultancy: Merck; Advisory/Consultancy: Bavarian Nordic; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy: Mirati; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Nektar Therapeutics; Advisory/Consultancy: Pfizer. P. Sharma: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Oncolytics; Advisory/Consultancy, Shareholder/Stockholder/Stock options, Licensing/Royalties: Jounce; Advisory/Consultancy, Shareholder/Stockholder/Stock options: BioAtla; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Forty-Seven; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Polaris; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Marker; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Codiak; Advisory/Consultancy, Shareholder/Stockholder/Stock options: ImaginAB; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Hummingbird; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Dragonfly; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Lytix; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Lava Therapeutics; Advisory/Consultancy: Infinity; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Achelois; Shareholder/Stockholder/Stock options: Constellation; Shareholder/Stockholder/Stock options: Apricity Health; Shareholder/Stockholder/Stock options: Neon. N. Tannir: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Exelixis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Nektar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Eisai Medical Research; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ono Pharmaceutical; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Oncorena; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Surface Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Neoleukin Therapeutics; Research grant/Funding (self): Calithera Bioscience; Research grant/Funding (self): Mirati Therapeutics; Research grant/Funding (self): Ar Pharmaceuticals; Research grant/Funding (self): Takeda; Research grant/Funding (self): Epizyme. All other authors have declared no conflicts of interest.