June 8, 2012 -- Roche's Erivedge, newly approved for advanced basal cell carcinoma, is "the greatest advance in therapy yet seen for this disease," according to an editorial in the New England Journal of Medicine.
"It is a landmark day for patients with basal cell carcinoma and all those involved in their care," wrote John Lear, MD, of the U.K.'s Manchester University.
It's also a landmark day for Anthony Oro, MD, PhD, of Stanford University. Oro was a postdoctoral student working on a then-obscure signaling pathway nicknamed sonic hedgehog. Hedgehog, it turned out, makes basal cell carcinoma and other tumors grow. Erivedge blocks hedgehog signals.
"The reason I have this excitement is I was there when this was discovered," Oro tells WebMD in an emotional interview. "That is rare for a scientist: to watch it go from a lab discovery to a drug, and then as a physician, treat patients with that drug. It is very rewarding."
Enthusiastic editorials such as Lear's and emotional interviews such as Oro's aren't usual responses to reports in a staid medical journal. But the reports themselves are unusual, especially in the field of cancer treatment.
The findings of one of these studies -- Oro is among the study leaders -- led the FDA last January to approve Erivedge for the treatment of advanced basal cell carcinoma (BCC) not treatable with surgery.
Although advanced BCC is rare, there's hope that Erivedge or other future hedgehog inhibitors might be useful in other deadly cancers.
"We know that there are other hedgehog-dependent cancers," Oro says. "Hedgehog is involved in pancreatic cancer and small-cell lung cancer, for example, and researchers are trying the drugs on those cancers."
Erivedge Effective for Advanced Basal Cell Carcinoma
BCC is the most common of all skin cancers. It's slow growing and is often cured by cutting it away. But rarely, the tumors are so advanced or in such bad places that surgery isn't an option. Even more rarely, BCC tumors spread to other parts of the body; again surgery isn't an option. And until last January, there was no other option.
Erivedge approval was based on a phase 2 trial. Larger, placebo-controlled phase 3 studies usually are needed for approval. But the FDA was impressed by the study results:
- Among 63 patients with locally advanced BCC, 13 had complete remissions.
- Overall, 43% of the patients with locally advanced BCC responded to treatment, usually within months.
- Among 33 patients with metastatic BCC, 30% responded to treatment.
Another study appearing in NEJM looked at people with a rare genetic mutation that causes them to develop hundreds or even thousands of BCC tumors. It's called basal-cell nevus syndrome or Gorlin syndrome. Erivedge cut the average number of new tumors per year from 29 to two, and reduced the size of existing tumors.
It would have been even better if all patients were fully cured. But for a cancer drug, the results are remarkable.
Erivedge Side Effects, Cost
There is of course a downside. Hedgehog is an important signaling pathway. Blocking it causes serious side effects. Overall, 12% of patients in the advanced BCC study had to stop taking the drug. And seven patients died during the clinical trial, although none of the deaths were attributed to side effects.
The Erivedge label carries a "black box" warning of the potential risks of death and severe birth defects if the drug is taken by pregnant women. Side effects of Erivedge include:
- Muscle spasms, some of them severe.
- Altered taste. "Food becomes tinny tasting," Oro says. "Often we see weight loss because patients don't eat as much. For cancer patients, this is not a good thing."
- Hair loss (strong hedgehog signaling is needed to maintain hair growth).
- Weight loss.
Has Erivedge approval made a big impact on cancer treatment? It's too soon to say, given that relatively few patients develop advanced BCC.
"The new medication will not affect the common approach to basal cell carcinoma treatment, which is surgery," Brown University's Martin Weinstock, MD, PhD, tells WebMD. "It is the very unusual case that would merit treatment with this." Weinstock was not involved in the Erivedge studies.
Erivedge treatment costs about $75,000 for a 10-month course of treatment.