1091PD - COMBI-d: Quality of Life (QOL) impact of the combination of dabrafenib and trametinib (D+T) versus dabrafenib monotherapy (D) in patients with BRAF...

Date 29 September 2014
Event ESMO 2014
Session Melanoma and other skin tumours
Topics Anti-Cancer Agents & Biologic Therapy
Melanoma and other Skin Tumours
Personalised Medicine
Presenter Dirk Schadendorf
Citation Annals of Oncology (2014) 25 (suppl_4): iv374-iv393. 10.1093/annonc/mdu344
Authors D. Schadendorf1, M.M. Amonkar2, D. Stroyakovskiy3, E. Levchenko4, H. Gogas5, F.G.M. De Braud6, J. Grob7, I. Bondarenko8, C. Garbe9, C. Lebbe10, J. Larkin11, V. Chiarion Sileni12, M. Millward13, A. Arance14, M. Mandalà15, M. Casey16, D. Demarini17, J. Irani18, G. Aktan19, G.V. Long20
  • 1Dermatology, University Hospital Essen, 45122 - Essen/DE
  • 2Value, Evidence And Outcomes (veo), GlaxoSmithKline, Collegeville/US
  • 3Chemotherapy, Moscow City Oncology Hospital #62, Moscow/RU
  • 4Thoracic Oncology, Petrov Research Institution of Oncology, 197758 - St. Petersburg/RU
  • 51st Department Of Medicine, University of Athens, GR-115 27 - Athens/GR
  • 6Division Of Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 7Dermatology And Skin Cancers, Hospital Timone, Marseille/FR
  • 8Oncology, Dnepropetrovsk State Medical Academy, Dnepropetrovsk/UA
  • 9Dermatology, University of Tübingen, Tübingen/DE
  • 10Cic, Dermatology, Hopital Saint Louis APHP, Paris/FR
  • 11Medical Oncology, Royal Marsden NHS Foundation Trust, - - London/GB
  • 12Medical Oncology ( Melanoma Unit), Veneto Oncology Institute, Padova/IT
  • 13Medical Oncology, Sir Charles Gardner Hospital, Perth/AU
  • 14Medical Oncology, Hospital Clinic, Barcelona/ES
  • 15Hematology And Oncology, Papa Giovanni XXIII, Bergamo/IT
  • 16Clinical Statistics, GlaxoSmithKline, Collegeville/US
  • 17Oncology, GlaxoSmithKline, Collegeville/US
  • 18Pcps, GlaxoSmithKline, Collegeville/US
  • 19Clinical Development, GlaxoSmithKline, Collegeville/US
  • 20The University Of Sydney And The Mater Hospital, Melanoma Institute Australia, 2060 - Sydney/AU

 

Abstract

Aim

COMBI-d is a double-blinded, randomized phase III study (NCT01584648) that demonstrated a statistically significant improvement in PFS (HR = 0.75; 95% CI 0.57–0.99; P = 0.035), and overall response rate (ORR) (67% vs. 51%; P = 0.0015) for D + T vs. D in patients with BRAF V600E/K unresectable or metastatic melanoma. This analysis presents the impact of treatments on QOL.

Methods

QOL was assessed using the EORTC QLQ-C30, a self-reporting generic cancer questionnaire (completed at baseline, during study treatment, at progression and post-progression). It assesses various dimensions, including global health/QOL, functional status and symptom impact. A mixed-model, repeated measures analyses of covariance assessed differences between arms.

Results

Questionnaire completion rates (as % of available subjects) were >90% at baseline and at weeks 8, 16, 24 and 32, and 71% at progression. At baseline, patients in both treatment arms reported comparable scores for all dimensions. The global health/QOL dimension was consistently better (significantly at weeks 8, 16 and 24) for patients receiving D + T compared with those receiving D during treatment and at progression. For functional dimensions (physical, social, role, emotional, and cognitive functioning) the majority of scores trended in favor of patients receiving D + T. In terms of symptom impact, pain scores were significantly improved and clinically meaningful (6–13 point difference) for patients receiving D + T compared with those receiving D for all follow-up assessments. For other symptom dimensions (nausea and vomiting, diarrhea, dyspnea and constipation), scores trended in favor of D.

Dimension Change from baseline to week/visit
8 16 24 32 Progression
Global health/QOL +* +* +* + +
Functioning
Cognitive +
Emotional + + + + +
Physical + +* + + +
Role + + +* +* +
Social + + + +* +
Symptoms
Appetite Loss + +
Constipation +
Diarrhea
Dyspnea
Fatigue + + + +
Insomnia + + + + +
Nausea and vomiting –* –*
Pain +* +* +* +* +*

+ favors D + T;–favors D; *P < 0.05.

Conclusions

In addition to the superior PFS and ORR of D + T vs. D, this analysis demonstrates that the combination provides further patient benefit based on global health/QOL and pain improvements.

Disclosure

D. Schadendorf: D.S. has received case money from GSK. D.S. has received personal fees and non-financial support from GSK, Roche, Novartis, Amgen, Merck/MSD and received a grant from Merck/MSD M.M. Amonkar: M.M.A is an employee of GSK and owns stock in GSK; H. Gogas: H.G. has received personal fees from BMS, Roch, Merck, Novartis and Amgen; J.-. Grob: J-J.G. received personal fees from GSK, Roche, NMS, Merck, Celgene and Novartis; C. Garbe: C.G. has received grants and personal fees from GSK and Roche. C.G. has received personal fees from MSD, Novartis and Philogen; C. Lebbe: C.L. has received personal fees for participation in advisory boards from GSK, Roche, BMS and Novartis; J. Larkin: J.L. has received grants and personal fees from Novartis and Pfizer. J.L. has received personal fees from BMS and GSK; V. Chiarion-Sileni: V.C-S. has received fees from GSK, BMS and Roche for participating in advisory boards; M. Millward: M.M. has received clinical trial payments from GSK. M.M. has received personal fees for participating in an advisory board; A. Arance: A.A. has received a grant, personal fees and non-financial support from GSK. A.A. has received a grant and personal fees from Roche. A.A. has received personal fees from BMS; M. Casey: M.C. is an employee of GSK and owns stock in GSK; D.J. Demarini: D.J.DeM. is an employee of GSK. D.J.DeM. has an issued patent for Pharmaceutical Composition Containing Trametinib. D.J.DeM. has a patent pending for Combinations of Mekinist + gemcitabine; J. Irani: J.I. is an employee of GSK; G. Aktan: G.A. is an employee of GSK. G.A. owns stock in GSK; G.V. Long: Trial conducted at G.V.L.'s institution, sponsored by GSK. G.V.L. has received personal fees as a consultant advisor for Roche, GSK and Novartis. All other authors have declared no conflicts of interest.