Entry Detail
| General information | |
| Database: | DB00964 |
| Objective: | Vemurafenib induces tumour regression in most patients with BRAF(V600E)mutant melanoma; eventually, most experience progressive disease (PD). Longterm followup of patients with BRAF(V600E) melanoma treated in the phase 1 vemurafenib trial is reported |
| Authors: | Puzanov I, et al |
| Title: | Longterm outcome in BRAF(V600E) melanoma patients treated with vemurafenib: Patterns of disease progression and clinical management of limited progression. |
| Journal: | Eur J Cancer. |
| Year: | 2015 |
| PMID: | 25980594 |
| Trial Design | |
| Clinical Trial Id: | NCT00405587 |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | melanoma |
| Cancer Subtype: | BRAF V600Emutant melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase I trial |
| Key Patients Feature: | patients with BRAF(V600E) melanoma |
| Biomarker: | BRAF(V600E) mutated |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received vemurafenib 2401120 mg (dose escalation cohort) or 960 mg (extension cohort) orally twice daily. Clinical response was evaluated every 8 weeks by Response Evaluation Criteria In Solid Tumors (RECIST). Patients with PD amenable to local therapy (surgery or radiotherapy) were allowed to continue vemurafenib after progression. Overall survival (OS) from time of treatment initiation and from PD was estimated. Sites of PD were recorded. |
| Primary End Point: | OS and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 48 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.2 months (range, 0.9-56.0). |
| Median OS A vs. C: | 14 months (range, 1.256.1) overall and 26.0 months (range, 7.756.1) among 20 patients who continued vemurafenib after local therapy. |
| Adverse Event(agent arm): | The most common AEs reported by 20% of the total population (N = 48) included arthralgia (64.6%), fatigue (62.5%), rash (58.3%), alopecia (52.1%), photosensitivity (45.8%), nausea (45.8%), diarrhoea (37.5%), vomiting (33.3%), squamous cell carcinoma of the skin (33.3%), palmar-plantar erythrodysesthesia syndrome (31.3%), pyrexia (31.3%), myalgia (31.3%), anorexia (31.3%), hyperglycaemia (29.2%), headache (29.2%), cough (27.1%), extremity pain (27.1%), dry skin (27.1%), pruritus (27.1%), peripheral oedema (27.1%), constipation (25.0%), hypokalaemia (25.0%), sunburn (22.9%), hypercholesterolaemia (22.9%), hyperkeratosis (22.9%), weight decrease (22.9%), skin papilloma (20.8%), hypertriglyceridaemia (20.8%) and hyponatraemia (20.8%). |
| Conclusions: | Some patients with melanoma achieved longterm survival with vemurafenib monotherapy. Continuation of vemurafenib after PD might be beneficial in some patients because remaining disease might continue to respond to BRAF inhibition |