Advances in skin cancer R&D

The last week has seen notable advances in the field of skin cancer research and development, including the initiation of Plexxikon's pivotal Phase III trial of PLX4032 in patients with metastatic melanoma (MM), detailed results of Biofrontera's Phase III comparative study of BF-200 ALA for the treatment of actinic keratosis (AK) and a new study from Stanford University suggesting that an anti-inflammatory prescription drug can reduce the risk of a common skin cancer in humans.

Enrolment has been initiated and the first patient has been dosed in the pivotal Phase III trial of PLX4032, a novel, oral and highly-targeted drug that is designed to inhibit the BRAF cancer-causing mutation that occurs in approximately 50 per cent of melanomas. The randomised, controlled trial, called BRIM3 (BRAF Inhibitor in Melanoma), in previously-untreated patients is part of the planned registration programme for PLX4032. With some tumour shrinkage in nearly all mutation-positive melanoma patients, and 70 per cent of patients achieving at least 30 per cent tumour shrinkage in the company's most recent clinical study, PLX4032 has shown meaningful antitumour activity. BRIM3 is expected to enrol approximately 700 previously-untreated melanoma patients who will be randomised 1:1 with PLX4032 960mg twice daily or dacarbazine.

Separately, detailed results of Biofrontera's Phase III comparative study have confirmed the superiority of BF-200 ALA over Photocure's Metvix (methylaminolevulinate) for the treatment of AK. Patients were treated by photodynamic therapy, combining one of the test compounds or a placebo with a brief red light illumination. With different types of red light sources, BF-200 ALA on average erased all lesions in 78 per cent of the patients, whereas the registered comparator, methylaminolevulinate, only reached a complete healing rate of 64 per cent, and the placebo group of 17 per cent.

Further, according to researchers at Stanford University School of Medicine, a widely-available anti-inflammatory prescription drug can reduce the risk of a common skin cancer in humans. The scientists believe that although oral administration of celecoxib is associated with an increased risk of myocardial infarction and stroke in some people, it is possible that topical application could have a safer, protective effect for people prone to developing basal cell carcinomas (BCCs). The investigators dovetailed studies in mice with a randomised, double-blind, Phase II trial to reach their conclusions.

The researchers enrolled 60 people with a genetic predisposition to BCC in a three-year trial. Approximately half of the patients received celecoxib 200mg twice daily in a tablet format, while the others received a placebo. All patients were monitored at three-month intervals at one of four study sites for the development of new BCCs or the growth of previously-identified cancers. They found that, although both groups continued to develop new cancers during the study, oral celecoxib treatment decreased the growth of skin tumours by approximately 50 per cent, as compared to placebo, in participants who entered the trial with 15 or fewer BCCs. Celecoxib treatment also reduced the overall tumour burden in this group of patients.

Alice Rossiter
Editor, Cancer Drug News