Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center

Aaron Lisberg; D Andrew Tucker; Jonathan W Goldman; Brian Wolf; James Carroll; Ariana Hardy; Karolyn Morris; Paulina Linares; Carlos Adame; Marshall L Spiegel; Courtney Wells; Jordan McKenzie; Blanca Ledezma; Melody Mendenhall; Phillip Abarca; Krikor Bornazyan; Jaime Hunt; Nima Moghadam; Natalie Chong; Danielle Nameth; Caitlin Marx; John Madrigal; Sitaram Vangala; Narek Shaverdian; David Elashoff; Edward B Garon

doi:10.1158/2326-6066.CIR-17-0063

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Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center

Journal article

Open access

Peer reviewed

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center

Aaron Lisberg, D Andrew Tucker, Jonathan W Goldman, Brian Wolf, James Carroll, Ariana Hardy, Karolyn Morris, Paulina Linares, Carlos Adame, Marshall L Spiegel, …

Cancer immunology research, Vol.6(3), pp.288-294

03/2018

DOI: 10.1158/2326-6066.CIR-17-0063

PMCID: PMC6066474

PMID: 29382669

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https://doi.org/10.1158/2326-6066.CIR-17-0063View

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Abstract

We retrospectively analyzed non-small cell lung cancer (NSCLC) patients from a single center treated with pembrolizumab on the KEYNOTE-001 trial and evaluated the association between treatment-related adverse events (trAEs) and clinical outcomes. Investigators reported AEs on trial and graded them according to Common Terminology Criteria for Adverse Events v4.0, labeling them as unlikely, possibly, or probably treatment-related. AEs labeled as possibly/probably related were considered trAEs for this analysis. The relationship between the incidence of a trAE and clinical outcomes was evaluated. Ninety-seven NSCLC patients treated on KEYNOTE-001 at the University of California, Los Angeles were evaluated. Ten percent (85/826) of AEs were trAEs, occurring in 40% (39/97) of patients. The most frequent trAEs were rash (21% patients), fatigue (6% patients), and hypothyroidism (6% patients). The 39 patients that experienced a trAE had increased objective response rate (ORR, 38.5%), progression-free survival (PFS: median, 248 days), and overall survival (OS: median, 493 days), compared with the 58 patients that did not (ORR: 8.9%, PFS: median 60 days, OS: median 144.5 days). The observed association between trAEs and improved clinical outcome persisted when using Cox proportional hazards regression models to assess the confounding effect of covariates and mitigate guarantee-time bias. The association also remained when data were substratified by grade, degree of association, and treatment-related select AE designation. This single-center analysis revealed that trAEs predicted for improved clinical outcome with pembrolizumab, and when controlling for guarantee-time bias and plausible confounders, this association remained. This observed relationship adds to our understanding of anti-PD-1 therapy and could aid clinicians in identifying patients most likely to benefit from therapy. .

Adult

Aged

Aged, 80 and over

Antibodies, Monoclonal, Humanized - adverse effects

Antineoplastic Agents, Immunological - adverse effects

Carcinoma, Non-Small-Cell Lung - drug therapy

Exanthema - chemically induced

Fatigue - chemically induced

Female

Humans

Hypothyroidism - chemically induced

Lung Neoplasms - drug therapy

Male

Middle Aged

Programmed Cell Death 1 Receptor - antagonists & inhibitors

Treatment Outcome

Details

Title: Subtitle: Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center
Creators: Aaron Lisberg - University of California, Los Angeles
D Andrew Tucker - University of California, Los Angeles
Jonathan W Goldman - University of California, Los Angeles
Brian Wolf - University of California, Los Angeles
James Carroll - University of California, Los Angeles
Ariana Hardy - University of California, Los Angeles
Karolyn Morris - University of California, Los Angeles
Paulina Linares - University of California, Los Angeles
Carlos Adame - University of California, Los Angeles
Marshall L Spiegel - University of California, Los Angeles
Courtney Wells - University of California, Los Angeles
Jordan McKenzie - University of California, Los Angeles
Blanca Ledezma - University of California, Los Angeles
Melody Mendenhall - University of California, Los Angeles
Phillip Abarca - University of California, Los Angeles
Krikor Bornazyan - University of California, Los Angeles
Jaime Hunt - University of California, Los Angeles
Nima Moghadam - University of California, Los Angeles
Natalie Chong - University of California, Los Angeles
Danielle Nameth - University of California, Los Angeles
Caitlin Marx - University of California, Los Angeles
John Madrigal - University of California, Los Angeles
Sitaram Vangala - University of California, Los Angeles
Narek Shaverdian - University of California, Los Angeles
David Elashoff - University of California, Los Angeles
Edward B Garon - University of California, Los Angeles
Resource Type: Journal article
Publication Details: Cancer immunology research, Vol.6(3), pp.288-294
DOI: 10.1158/2326-6066.CIR-17-0063
PMID: 29382669
PMCID: PMC6066474
ISSN: 2326-6066
eISSN: 2326-6074
Grant note: R01 CA208403 / NCI NIH HHS P30 CA016042 / NCI NIH HHS UL1 TR001881 / NCATS NIH HHS
Language: English
Date published: 03/2018
Academic Unit: Orthopedics and Rehabilitation; Physical Therapy and Rehabilitation Science
Record Identifier: 9984295053602771

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