Patient perception of the benefit of a BRAF inhibitor in metastatic melanoma: quality-of-life analyses of the BREAK-3 study comparing dabrafenib with dacarbazine.
BACKGROUND
In a randomized phase III study (BREAK-3), dabrafenib showed prolonged progression-free survival (PFS) (median 5.1 versus 2.7 months; hazard ratio = 0.30; 95% confidence interval 0.18-0.53; P < 0.0001) compared with dacarbazine (DTIC) in patients with BRAF V600E metastatic melanoma. Assessing how these results are transformed into a real health benefit for patients is crucial.


METHODS
The EORTC QLQ-C30 questionnaire assessed quality of life (QoL) at baseline and follow-up visits.


RESULTS
For DTIC, all functional dimensions except role dimension worsened from baseline at follow-up. For dabrafenib, all functionality dimensions remained stable relative to baseline or improved at week 6; mean change in seven symptom dimensions improved from baseline, with appetite loss, insomnia, nausea and vomiting, and pain showing the greatest improvement. In the DTIC arm, symptom dimensions were unchanged or worsened from baseline for all symptoms except pain (week 6), with the greatest exacerbations observed for fatigue and nausea and vomiting. Mixed-model-repeated measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements from baseline in favor of dabrafenib for emotional and social functioning, nausea and vomiting, appetite loss, diarrhea, fatigue, dyspnea, and insomnia at weeks 6 and/or 12. After crossing over to dabrafenib upon progression (n = 35), improvements in all QoL dimensions were evident after receiving dabrafenib for 6 (n = 31) to 12 (n = 25) weeks.


CONCLUSIONS
This first reported QoL analysis for a BRAF inhibitor in metastatic melanoma demonstrates that the high tumor response rates and PFS superiority of dabrafenib over DTIC is not only a theoretical advantage, but also transforms in a rapid functional and symptomatic benefit for the patient. ClinicalTrials.gov Identifier: NCT01227889.
Aix-Marseille University, APHM, Hôpital Timone, Marseille, France. Electronic address: jean-jacques.grob@ap-hm.fr.
J-J
JJ
Grob
GlaxoSmithKline, Collegeville, USA.
M M
MM
Amonkar
Department of Medical Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
S
S
Martin-Algarra
Department of Tumor Biotherapy, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation.
L V
LV
Demidov
GlaxoSmithKline, Collegeville, USA.
V
V
Goodman
GlaxoSmithKline, Collegeville, USA.
K
K
Grotzinger
GlaxoSmithKline, Collegeville, USA.
P
P
Haney
Department of Dermatology, Skin Cancer Center, University Hospital Erlangen, Erlangen, Germany.
E
E
Kämpgen
Przychodnia Lekarska KOMED, Konin, Poland.
B
B
Karaszewska
Department for Dermatology and Venereology and CIO KölnBonn, University Hospital Cologne, Cologne, Germany.
C
C
Mauch
Departments of Oncology and Medicine, Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Canada.
W H
WH
Miller
Department of Medical Oncology, Sir Charles Gairdner Hospital and School of Medicine and Physiology, University of Western Australia, Perth, Australia.
M
M
Millward
GlaxoSmithKline, Collegeville, USA.
B
B
Mirakhur
Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
P
P
Rutkowski
Melanoma Cancer Unit, Veneto Oncology Institute-IRCCS, Padova, Italy.
V
V
Chiarion-Sileni
GlaxoSmithKline, Collegeville, USA.
S
S
Swann
Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.
A
A
Hauschild
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003606:Dacarbazine / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D010091:Oximes / Q000627:therapeutic use*; D011788:Quality of Life
D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; D003606:Dacarbazine; C561627:dabrafenib
BRAF; chemotherapy; dabrafenib; melanoma; quality of life