Schadendorf Dirk, Amonkar Mayur M, Stroyakovskiy Daniil, Levchenko Evgeny, Gogas Helen, de Braud Filippo, Grob Jean-Jacques, Bondarenko Igor, Garbe Claus, Lebbe Celeste, Larkin James, Chiarion-Sileni Vanna, Millward Michael, Arance Ana, Mandalà Mario, Flaherty Keith T, Nathan Paul, Ribas Antoni, Robert Caroline, Casey Michelle, DeMarini Douglas J, Irani Jhangir G, Aktan Gursel, Long Georgina V
Universitätsklinikum Essen, Hufelandstr. 55, Essen 45147, Germany.
GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States.
Eur J Cancer. 2015 May;51(7):833-40. doi: 10.1016/j.ejca.2015.03.004. Epub 2015 Mar 17.
To present the impact of treatments on health-related quality of life (HRQoL) from the double-blind, randomised phase III COMBI-d study that investigated the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600E/K-mutant metastatic melanoma. COMBI-d showed significantly prolonged progression-free survival for the combination.
HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, a generic cancer questionnaire (completed at baseline, during study treatment, at progression and post progression) assessing various dimensions (global health/QoL, functional status, and symptom impact). A mixed-model, repeated-measures analyses of covariance evaluated differences between arms.
Questionnaire completion rates were >95% at baseline, >85% to week 40 and >70% at disease progression. Baseline scores across both arms were comparable for all dimensions. Global health dimension scores were significantly better at weeks 8, 16 and 24 for patients receiving the combination during treatment and at progression. The majority of functional dimension scores (physical, social, role, emotional and cognitive functioning) trended in favour of the combination. Pain scores were significantly improved and clinically meaningful (6-13 point difference) for patients receiving the combination for all follow-up assessments versus those receiving dabrafenib monotherapy. For other symptom dimensions (nausea and vomiting, diarrhoea, dyspnoea, and constipation), scores trended in favour of dabrafenib monotherapy.
This analysis demonstrates that the combination of dabrafenib and trametinib provides better preservation of HRQoL and pain improvements versus dabrafenib monotherapy while also delaying progression. (Clinicaltrials.gov registration number: NCT01584648).
呈现双盲、随机III期COMBI-d研究中治疗对健康相关生活质量（HRQoL）的影响，该研究调查了达拉非尼与曲美替尼联合用药对比达拉非尼单药治疗BRAF V600E/K突变转移性黑色素瘤患者的疗效。COMBI-d研究显示联合用药显著延长了无进展生存期。
使用欧洲癌症研究与治疗组织生活质量问卷-C30评估HRQoL，这是一份通用癌症问卷（在基线、研究治疗期间、病情进展时和病情进展后完成），评估多个维度（总体健康/生活质量、功能状态和症状影响）。采用混合模型重复测量协方差分析评估两组之间的差异。
基线时问卷完成率>95%，第40周时>85%，疾病进展时>70%。两组所有维度的基线得分相当。在治疗期间和病情进展时接受联合用药的患者，在第8周、16周和24周时总体健康维度得分显著更高。大多数功能维度得分（身体、社会、角色、情感和认知功能）倾向于联合用药。在所有随访评估中，接受联合用药的患者与接受达拉非尼单药治疗的患者相比，疼痛得分显著改善且具有临床意义（相差6-13分）。对于其他症状维度（恶心和呕吐、腹泻、呼吸困难和便秘），得分倾向于达拉非尼单药治疗。
该分析表明，与达拉非尼单药治疗相比达拉非尼与曲美替尼联合用药能更好地维持HRQoL并改善疼痛，同时还能延缓病情进展。（Clinicaltrials.gov注册号：NCT01584648）
