CHMP Favors Kadcyla Approval in EU for Certain HER2-positive Early Breast Cancer Patients

The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency, has recommended that Kadcyla (ado-trastuzumab emtansine) be approved as an adjuvant (post-surgery) treatment for certain HER2-positive early breast cancers, the treatment’s maker, Genentech, has announced.

Specifically, the advisory committee for the European Union’s regulatory agency is recommending Kadcyla’s approval for patients who still have residual disease in their breast or lymph nodes after receiving pre-surgery treatment with a taxane and HER2-targeted therapy, such as trastuzumab.

In the coming months, the European Commission is expected to decide whether or not to expand the existing marketing authorization for Kadcyla in the EU, based on CHMP’s recommendation.

The U.S. Food and Drug Administration granted the treatment accelerated approval for a similar indication in May, 12 weeks after a submission had been filed.

“In the early breast cancer setting where cure is achievable, it is important to do everything possible to prevent progression to an advanced, incurable stage,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, which owns Genentech, said in a press release. “This recommendation therefore marks a significant step forward in bringing a potentially transformative treatment option to patients in Europe with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant therapy.”

People with early breast cancer are often treated with chemotherapy regimens both before and after their breast cancer surgery. While the pre-surgical treatment is intended to reduce tumor size and improve surgical outcomes, post-surgery treatment aims to eliminate any traces of cancer cells that remain after surgery to reduce the chances of relapse.

When breast cancer cells are driven by the HER2 protein, which acts to send signals that drive excessive cell growth, the HER2 antibody trastuzumab (marketed as Herceptin and Ogivri, among others) is often added to chemotherapy to improve patient outcomes.

But in cases where cancer cells remain in the breast or lymph nodes after trastuzumab-containing adjuvant chemotherapy, targeting HER2 through a different mechanism in the post-surgery setting may offer patients a better chance of survival.

CHMP’s recommendation was based on data from the KATHERINE Phase 3 trial (NCT01772472), which examined if Kadcyla — containing trastuzumab bound to a toxic payload — would be better than Herceptin at delaying breast cancer recurrence in this setting.

The trial enrolled 1,486 HER2-positive, early-stage breast cancer patients who had residual cancer cells after neoadjuvant (before surgery) treatment with taxane-based chemotherapy and trastuzumab.

Patients were randomly assigned Kadcyla or Herceptin, given as into-the-vein injections every three weeks for 14 cycles.

KATHERINE showed that Kadcyla significantly improved survival outcomes for these breast cancer patients, reducing their risk of breast cancer recurrence or death from any cause by 50% — the trial’s main goal.

At three years, 88.3% of patients on Kadcyla were alive and their cancer had not returned, compared with 77% of those on Herceptin. Kadcyla also lowered the risk of metastatic disease or death by 40%.

Kadcyla’s safety profile was similar to that seen in other trials, with common serious adverse side effects including low platelet counts and high blood pressure.

Kadcyla is also approved in more than 100 countries, including the U.S. and EU, for HER2-positive advanced breast cancer patients who received prior therapy with a taxane chemotherapy agent and trastuzumab.