Health-related quality of life in the randomised KEYNOTE-002 study of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory melanoma.
In KEYNOTE-002, pembrolizumab significantly prolonged progression-free survival and was associated with a better safety profile compared with chemotherapy in patients with advanced melanoma that progressed after ipilimumab. We present health-related quality of life (HRQoL) outcomes from KEYNOTE-002.



Patients were randomly assigned 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or investigator-choice chemotherapy. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 instrument. A constrained longitudinal data analysis model was implemented to assess between-arm differences in HRQoL scores. The study is registered with ClinicalTrials.gov, number NCT01704287.



Of the 540 patients enrolled, 520 were included in the HRQoL analysis. Baseline global health status (GHS) was similar across treatment arms. Compliance rates at week 12 were 76.6% (n = 108), 82.3% (n = 121), and 86.4% (n = 133) for the control, pembrolizumab 2 mg/kg Q3W, and pembrolizumab 10 mg/kg Q3W arms, respectively. From baseline to week 12, GHS/HRQoL scores were maintained to a higher degree in the pembrolizumab arms compared with the chemotherapy arm (decrease of -2.6 for each pembrolizumab arm versus -9.1 for chemotherapy; P = 0.01 for each pembrolizumab arm versus chemotherapy). Fewer patients treated with pembrolizumab experienced deterioration in GHS at week 12 (31.8% for pembrolizumab 2 mg/kg, 26.6% for 10 mg/kg, and 38.3% for chemotherapy), with similar trends observed for the individual functioning and symptoms scales.



HRQoL was better maintained with pembrolizumab than with chemotherapy in KEYNOTE-002, supporting the use of pembrolizumab in patients with ipilimumab-refractory melanoma.
University Hospital Essen, Hufelandstrasse 55, D-45147 Essen, Germany. Electronic address: dirk.schadendorf@uk-essen.de.
Dirk
D
Schadendorf
Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland. Electronic address: Reinhard.Dummer@usz.ch.
Reinhard
R
Dummer
Department of Dermatology, Venereology, and Allergology, University Hospital Schleswig-Holstein, Kiel Campus, Arnold-Heller Strasse 3, 24105 Kiel, Germany. Electronic address: ahauschild@dermatology.uni-kiel.de.
Axel
A
Hauschild
Gustave Roussy Cancer Campus and Paris-Sud University, 114 Rue Edouard Vaillant, 94800 Villejuif, France. Electronic address: Caroline.Robert@gustaveroussyr.fr.
Caroline
C
Robert
The Angeles Clinic and Research Institute, 2001 Santa Monica Blvd, Ste 560W, Santa Monica, CA 90404, USA. Electronic address: ohamid@theangelesclinic.org.
Omid
O
Hamid
University of California, San Francisco School of Medicine, 1600 Divisadero St, NZ Bldg A, San Francisco, CA 94115, USA. Electronic address: Adil.Daud@ucsf.edu.
Adil
A
Daud
Department of Medical Oncology, VU University Medical Center Amsterdam, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. Electronic address: vandeneertwegh@VUMC.nl.
Alfons
A
van den Eertwegh
Department of Hematology/Oncology, University of Arizona Cancer Center at UMC North, 3838 N. Campbell Ave, Tucson, AZ 85724, USA. Electronic address: lcranmer@uacc.arizona.edu.
Lee
L
Cranmer
The Los Angeles Skin Cancer Institute, The Beverly Hills Cancer Center, 8900 Wilshire Blvd, Beverly Hills, CA 90211, USA. Electronic address: stevenjoday@gmail.com.
Steven
S
O'Day
Vanderbilt-Ingram Cancer Center, 2220 Pierce Ave, 777 Preston Research Building, Nashville, TN 37232, USA. Electronic address: igor.puzanov@vanderbilt.edu.
Igor
I
Puzanov
Department of Oncology, Ella Institute for Melanoma, Sheba Medical Center, Derech Sheba 2, Tel-Hashomer, Ramat-Gan, Israel. Electronic address: Jacob.Schachter@sheba.health.gov.il.
Jacob
J
Schachter
Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: c.blank@nki.nl.
Christian
C
Blank
Division of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Box 3198, 20 Duke Medicine Circle, Durham, NC 27710, USA. Electronic address: april.salama@duke.edu.
April
A
Salama
Skin Clinic, Universitätsmedizin Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. Electronic address: carmen.loquai@unimedizin-mainz.de.
Carmen
C
Loquai
Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA. Electronic address: mehnerja@cinj.rutgers.edu.
Janice M
JM
Mehnert
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: darcy_hille@merck.com.
Darcy
D
Hille
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: scot_ebbinghaus@merck.com.
Scot
S
Ebbinghaus
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: s.peter.kang@merck.com.
S Peter
SP
Kang
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: wei.zhou2@merck.com.
Wei
W
Zhou
Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (JCCC) at the University of California, Los Angeles (UCLA), 10833 Le Conte Ave, Los Angeles, CA 90095, USA. Electronic address: aribas@mednet.ucla.edu.
Antoni
A
Ribas
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D000071066:Patient Reported Outcome Measures; D011788:Quality of Life; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077204:Temozolomide; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D003606:Dacarbazine; D016190:Carboplatin; C582435:pembrolizumab; D017239:Paclitaxel; D000077204:Temozolomide
Advanced melanoma; Chemotherapy; EORTC QLQ-C30; Health-related quality of life; Ipilimumab-refractory melanoma; KEYNOTE-002; Patient-reported outcomes; Pembrolizumab