| General information |
| Database: | DB00184 |
| Objective: | To present the impact of treatments on healthrelated quality of life (HRQoL) from the doubleblind, randomisedphase III COMBId study that investigated the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600E/Kmutant metastatic melanoma. COMBId showed significantly prolonged progression free survival for the combination. |
| Authors: | Schadendorf D, et al |
| Title: | Healthrelated quality of life impact in a randomisedphase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma. |
| Journal: | Eur J Cancer. |
| Year: | 2015 |
| PMID: | 25794603 |
| Trial Design |
| Clinical Trial Id: | NCT01584648 |
| Agent: | dabrafenib
|
| Target: | BRaf protooncogene serine/threonineprotein kinase
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | dabrafenib+ trametinib |
| Study Type: | a randomised, doubleblind, twoarm, internationalphase III study |
| Key Patients Feature: | patients with histologically confirmed, unresectable stage IIIC or stage IV melanoma with BRAF V600E or V600K mutations |
| Biomarker: | BRAFmutated |
| Biomark Analysis: | NA |
| Control Group Info: | dabrafenib alone |
| Treatment Info: | HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life QuestionnaireC30, 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). |
| Primary End Point: | investigatorassessed PFS. |
| Secondary End Point: | OS, response rate, response duration, safety, pharmacokinetics and HRQoL. |
| Patients Number: | 423 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | pain scores significantly improved and were clinically meaningful (symptom improved by a 6-13 point difference) for patients receiving the combination therapy |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Statistically significant improvements were observed in physical functioning at weeks 16 and 40, role functioning at weeks 24 and 32, social functioning at weeks 32 and 40, and cognitive functioning at week 40, and clinically meaningful improvements were observed in role functioning at weeks 24, 32, 40 and at disease progression, cognitive functioning at week 40, and social functioning at weeks 32 and 40 |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | scores were comparable in patients receiving the combination therapy and those receiving dabrafenib monotherapy, although fatigue and insomnia trended in favour of the combination, and nausea/vomiting, diarrhoea, dyspnoea and constipation trended in favour of dabrafenib monotherapy |
| Conclusions: | 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. |