XOFIGO AND KADCYLA NEAR APPROVAL BY EMA

In the European Union, the Committee for Medicinal Products for Human Use (CHMP) has recommended 2 novel cancer drugs for approval — trastuzumab emtansine (Kadcyla, Roche) for the treatment of metastatic breast cancer, and radium-223 chloride (Xofigo, Bayer) for the treatment of castration-resistant prostate cancer. Both have been shown to prolong survival.

This positive opinion from the CHMP is followed in 67 days by a decision from the European Commission on the approval.

Trastuzumab emtansine is a novel product comprised of theHER2-targeting monoclonal antibody trastuzumab linked to the cytotoxic agent DM1 (the product is also known as T-DM1). Itwas approved in the United States in February for use in patients with HER2-positive metastatic breast cancer who were previously treated with trastuzumab (Herceptin, Genentech/Roche) and a taxane chemotherapy. The indication in the EU approval application is similar.

This indication is based on results from the pivotal phase 3EMILIA study, which involved 991 patients and showed a significantly improved overall survival for those on the novel drug. Patients on trastuzumab emtansine survived nearly 6 months longer than patients receiving the standard therapy of lapatinib (Tykerb) plus capecitabine (Xeloda) (median overall survival, 30.9 vs 25.1 months), and also experienced fewer severe adverse (reported by 43.1% vs 59.2% with standard therapy).

Radium-223 chloride (formerly known as alpharadin) is also a novel product, an alpha-radiation emitter that preferentially targets bone. The indication in the European approval application is the same as that already approved in the United States in May, which is use in patients with castration-resistant prostate cancer who have symptomatic bone metastases, but no visceral metastases.

In the pivotal phase 3 ALSYMPCA trial, which involved 809 prostate cancer patients who were resistant to hormone treatment and had developed 2 or more bone metastases, men who received radium-223 chloride lived significantly longer than those who received standard therapy. An interim analysis revealed a median overall survival of 14.0 months, compared with 11.2 months (hazard ratio, 0.695;P = .00185), and the trial was stopped early because of benefit. An exploratory updated analysis confirmed the product's ability to extend overall survival, according to the US Food and Drug Administration.

Researchers reporting these results suggest that radium-223 chloride "may provide a new standard of care" for patients with castration-resistant prostate cancer and bone metastases.

Extension of Indications

In addition, the CHMP has recommended approval for an extension to the existing indication for the melanoma immunotherapy ipilimumab (Yervoy, Bristol-Myers Squibb), so that it can now be used as a first-line treatment. The approved indication had previously stipulated that ipilimumab was used in adults with advanced melanoma "who have received prior therapy," but this wording has now been removed, extending use of the drug to previously untreated patients, the CHMP said.

Another label change that was recommended concerns the use of everolimus (Votubia, Novartis) in the treatment of subependymal giant cell astrocytoma associated with tuberous sclerosis complex. Previously, the wording had stipulated that the indication covered use in patients "aged 3 years or older," but this wording has now been removed, allowing the drug to be used in younger children.

Further details on these CHMP decisions can be found at the European Medicines Agency Web site.