New gene-targeted drug offers hope in skin cancer

BERLIN (Reuters) - Scientists offered new hope in the fight against the most deadly type of skin cancer on Wednesday as an early-stage clinical trial showed an experimental drug dramatically shrank tumors.

This combination photo shows a scan at the start of a melanoma drug (PLX4032) trial (L), which Roche is developing with privately-held U.S. biotech company Plexxikon. The figure on the right shows a scan after 2 weeks of treatment. REUTERS/PLX4032 Phase 1 extension study/Handout

Another study also found Roche’s established cancer drug Avastin had promise in treating melanoma, but it failed to show a statistically significant improvement in survival.

Paul Chapman from the Memorial Sloan-Kettering Cancer Center in New York said 70 percent of patients with a particular gene mutation saw their tumors shrink when given the new pill, called PLX4032.

“To put that into context, chemotherapy is about 13 to 15 percent, and that’s where we have been stuck with conventional treatments,” he said at the ECCO-ESMO cancer congress in Berlin.

Of the 27 patients evaluated in the small Phase I study, two responded completely and signs of their disease disappeared.

Preliminary findings with the new drug were first reported in June but the data from more patients have boosted confidence in its prospects.

Chapman and his colleagues are planning a Phase II trial of 90 patients starting at the end of 2009, and a large international Phase III trial involving several hundred patients is planned to start in late 2009 or early 2010.

Alexander Eggermont, president of the European Cancer Organization, described the trial as “simply spectacular” and said it showed the benefits of targeting treatment.

The news would transform melanoma work into “a very exciting field instead of a graveyard,” he said.

PLX4032, which Roche is developing with privately-held U.S. biotech company Plexxikon, is the latest in a growing group of gene-targeted drugs that oncologists believe will drive future cancer treatment.

It blocks the activity of the cancer-causing mutation of the BRAF gene involved 50 to 60 percent of melanomas.

Eggermont said findings on BRAF status, which showed the some 40 percent of patients with the unmutated gene had no response to the drug, gave oncologists clearly defined targets.

“We know exactly what we are doing, that is what all the excitement is about,” he told reporters.

Malignant melanoma is the most serious type of skin cancer, with about 160,000 new cases diagnosed worldwide each year. It is treatable if caught early, but in patients whose disease has spread it is rarely cured and often kills them within a year.


The failure of Avastin -- a $5 billion-a-year seller in colon, lung and breast cancer -- confounded expectations of doctors in Berlin, since a late-breaking abstract published earlier had reported a meaningful survival benefit.

But a last-minute review of the clinical data changed the outcome and researchers said the Phase II study in fact missed its goal, despite an encouraging trend.

Medical experts said larger trials might yet prove Avastin worked in melanoma, noting that the drug also initially failed to show significance in breast cancer.

They also said there was a potential for combining Avastin with the new gene-targeted drug in future.

Despite the disappointment of the Avastin study, lead investigator Steven O’Day of the Angeles Clinic and Research Institute in California said the data collected on Avastin were “very encouraging and warrant continued investigation.”

The 214-patient study found the median overall survival in the Avastin arm was 12.3 months, against 9.2 months in the control arm, but there was a 19 percent likelihood that this result happened by chance.

To prove statistical significance, clinical trials must show a likelihood of 5 percent or less that a finding is due to chance.

Editing by Jon Loades-Carter