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

• Authors: Thomas M Atkinson, Memorial Sloan Kettering Cancer Center; Jennifer L. Hay, Memorial Sloan Kettering Cancer Center; Alexander Shoushtari, Memorial Sloan Kettering Cancer Center; Yuelin Li, Memorial Sloan Kettering Cancer Center; Daniel J. Paucar, Montefiore Medical Center; Sloane C. Smith, Memorial Sloan Kettering Cancer Center; Ragini R. Kudchadkar, Emory University; Austin Doyle, National Cancer Institute; Jeffrey Sosman, Northwestern University; Jorge Fernando Quevedo, Mayo Clinic; Mohammed M. Milhem, University of Iowa; Anthony M. Joshua, Princess Margaret Hospital; Gerald P. Linette, Penn Medicine; Thomas F. Gajewski, University of Chicago; Jose Lutzky, Mount Sinai School of Medicine; David H Lawson, Emory University; Christopher Lao, University of Michigan; Patrick J. Flynn, Minnesota Oncology; Mark R. Albertini, University of Wisconsin; Takami Sato, Thomas Jefferson University; Karl Lewis, University of Colorado; Brian Marr, Memorial Sloan Kettering Cancer Center; David Abramson, Memorial Sloan Kettering Cancer Center; Mark Andrew Dickson, Memorial Sloan Kettering Cancer Center; Gary Schwartz, Columbia University; Richard Carvajal, Columbia University
• Journal Title: Journal of Cancer Research and Clinical Oncology
• Volume: Volume 143, Number 3
• Publisher: Springer Verlag (Germany) | 2017-03-01, Pages 439-445
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s00432-016-2318-x
• Subjects: Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Patient-reported outcomes; Quality of life; Selumetinib; Neoplasms; Uveal melanoma; Adverse events; Clinical trials; COMMON TERMINOLOGY CRITERIA; FUNCTIONAL ASSESSMENT; CANCER-TREATMENT; OUTCOMES; THERAPY; CTCAE; PRO; CHEMOTHERAPY; ONCOLOGY; VERSION

Abstract

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.