Anti-PD1-Induced Immune-Related Adverse Events and Survival Outcomes in Advanced Melanoma.

Publication date: Feb 12, 2020

Objective response rates (ORR) appear to be higher in melanoma patients who develop immune-related adverse events (irAEs), but whether there is a similar association between irAEs and survival remains unknown.

Patients with advanced melanoma treated with single-agent pembrolizumab or nivolumab in the province of Alberta from June 2014 to May 2017 were identified through the provincial pharmacy database. Chart review identified and categorized all irAEs that occurred while on anti-programmed cell death protein 1 (PD-1) checkpoint inhibitors. The primary objective was to compare overall survival (OS) with patients who developed any irAEs versus those who did not. Secondary outcomes included progression-free survival (PFS) and ORR.

Among 186 patients, any-grade and grade ?3 irAEs occurred in 88 (47%) and 27 (15%) patients, respectively; one patient died of pneumonitis. In a landmark analysis excluding patients who died within the first 12?weeks, the median follow-up was 24 months, 20 months in patients without any irAEs and 26 months in patients with irAEs (p = .006). Median OS was 39 versus 23 months (hazard ratio [HR], 0.46; p = .001) for any irAE and no irAE, respectively, and median OS not reached versus 29 months for grade ?3 irAEs and no grade ?3 irAEs, respectively. In multivariate analysis, elevated lactate dehydrogenase correlated with reduced OS (HR, 2.34; p = .001), whereas each additional cycle of treatment received (HR, 0.94; p

Open Access PDF

Suo, A., Chan, Y., Beaulieu, C., Kong, S., Cheung, W.Y., Monzon, J.G., Smylie, M., Walker, J., Morris, D., and Cheng, T. Anti-PD1-Induced Immune-Related Adverse Events and Survival Outcomes in Advanced Melanoma. 25780. 2020 Oncologist.

Concepts Keywords
Alberta Checkpoint inhibitor
HR 2 Bristol-Myers Squibb
Lactate Dehydrogenase Cancer treatments
Median Breakthrough therapy
Melanoma Antineoplastic drugs
Multivariate Analysis Immune system
Oncologist Clinical medicine
Pharmacy Medicine
Pneumonitis Immunotherapy
Province Higher melanoma
Pneumonitis
Nivolumab
Pembrolizumab
Melanoma

Semantics

Type Source Name
disease MESH Melanoma
pathway KEGG Melanoma
drug DRUGBANK Pembrolizumab
drug DRUGBANK Nivolumab
pathway REACTOME Programmed Cell Death
disease MESH pneumonitis

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