title: Relationship between physician-adjudicated adverse events and patient-reported health-related quality of life in a phase II clinical trial (NCT01143402) of patients with metastatic uveal melanoma.
abstract: OBJECTIVE
  Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the common terminology criteria for adverse events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data are becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied.
  
  
  METHODS
  Data from a phase II trial (clinicaltrials.gov identifier: NCT01143402) where patients with metastatic uveal melanoma were randomized to receive selumetinib, an oral MEK inhibitor, or chemotherapy were analyzed. Patients reported HRQoL at baseline, after 1 month, and end of treatment (n = 118), whereas physicians adjudicated AEs via CTCAE. Mean HRQoL scores were compared between patient randomization arms, as well as between those patients who did/did not receive dose modifications.
  
  
  RESULTS
  Ninety-four percent had a CTCAE grade ≥1 for at least one treatment-associated AE, with 18% undergoing dose modification due to toxicity. Mean HRQoL scores did not significantly differ at each of the three time points. Patient and physician-adjudicated reports of nausea were significantly correlated at the start (r = 0.31, p < 0.01) and end of treatment (r = 0.42, p < 0.05). There were no significant correlations between need for dose modification and HRQoL scores.
  
  
  CONCLUSIONS
  Despite the high rate of physician-adjudicated AEs and need for dose modifications with selumetinib, patient-reported HRQoL was not impacted by treatment. Since HRQoL did not differ in the subgroup of patients who received dosage reductions due to AEs, patients may be willing to tolerate select AEs without dose modification (if medically appropriate). More research is needed to determine how to best integrate HRQoL data into clinical trial conduct.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY, 10022, USA. atkinsot@mskcc.org.
authors.forename: Thomas M
authors.identifier: http://orcid.org/0000-0002-4965-3913
authors.initials: TM
authors.lastname: Atkinson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY, 10022, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hay
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY, 10022, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shoushtari
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY, 10022, USA.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Paucar
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY, 10022, USA.
authors.forename: Sloane C
authors.initials: SC
authors.lastname: Smith
authors.affiliation: Winship Cancer Institute of Emory University, Atlanta, GA, USA.
authors.forename: Ragini R
authors.initials: RR
authors.lastname: Kudchadkar
authors.affiliation: Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Doyle
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Jorge Fernando
authors.initials: JF
authors.lastname: Quevedo
authors.affiliation: University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Milhem
authors.affiliation: Princess Margaret Hospital University Health Network, Toronto, ON, Canada.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
authors.affiliation: Penn Medicine, Philadelphia, PA, USA.
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Linette
authors.affiliation: University of Chicago, Chicago, IL, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
authors.affiliation: Mount Sinai Medical Center, Miami Beach, FL, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Lutzky
authors.affiliation: Winship Cancer Institute of Emory University, Atlanta, GA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Lawson
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lao
authors.affiliation: Minnesota Oncology, Woodbury, MN, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Flynn
authors.affiliation: Univeristy of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Albertini
authors.affiliation: Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Takami
authors.initials: T
authors.lastname: Sato
authors.affiliation: University of Colorado - Denver, Denver, CO, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Lewis
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY, 10022, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Marr
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY, 10022, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Abramson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY, 10022, USA.
authors.forename: Mark Andrew
authors.initials: MA
authors.lastname: Dickson
authors.affiliation: Columbia University Medical Center, New York, NY, USA.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schwartz
authors.affiliation: Columbia University Medical Center, New York, NY, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
mesh_terms: D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D010820:Physicians; D011788:Quality of Life; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: C517975:AZD 6244; D001562:Benzimidazoles
keywords: Adverse events; Clinical trials; Neoplasms; Patient-reported outcomes; Quality of life; Selumetinib; Uveal melanoma