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FDA Grants Priority Review to Genentech's Perjeta sBLA for Neo-Adjuvant HER2 Breast Cancer

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The US Food and Drug Administration has accepted a supplemental biologics license application for Perjeta (pertuzumab) as a neoadjuvant treatment for women with HER2-positive, early-stage breast cancer, Roche subsidiary Genentech announced this week.

A year ago, the agency approved Perjeta in combination with Herceptin and chemotherapy as a treatment for HER2-positive metastatic breast cancer (PGx Reporter 6/13/2012). The drug was approved with two companion diagnostics developed by Dako to help doctors gauge which patients have HER2-overexpressing tumors and should receive the drug.

Genentech is now seeking approval for the drug as an earlier option for HER2-positive breast cancer patients after they've been diagnosed with the disease and before they've undergone surgery.

"The impact of treatment in breast cancer is greatest in the early stage, before the cancer has spread to other parts of the body," Hal Barron, Roche's chief medical officer and head of global product development, said in a statement. By administering a drug neoadjuvantly, doctors aim to reduce the size of a tumor so it is easier to remove with surgery. The FDA has yet to approve neoadjuvant treatments for cancer.

For the sBLA, Genentech submitted data from two Phase II trials, called NEOSPHERE and TRYPHAENA, involving HER2-positive, early stage breast cancer patients. The company also submitted long-term safety data from the Phase III CLEOPATRA trial with HER2-positive metastatic breast cancer patients.

In the NEOSPHERE trial, more than 400 patients with newly diagnosed HER2-positive, locally advanced, early stage breast cancer were randomized to four neoadjuvant treatment arms: Herceptin and docetaxel; Perjeta, Herceptin, and docetaxel; Perjeta and Herceptin; and Perjeta and docetaxel.

Researchers gauged the efficacy of the treatment regimens by pathological complete response (pCR), which measures detectable tumor tissue at the time of surgery. In the Herceptin/docetaxel arm 29 percent of the patients had a pCR, nearly 46 percent had a pCR in the Perjeta/Herceptin/docetaxel arm; around 17 percent had a pCR in the Perjeta/Herceptin arm; and 24 percent had a pCR in the Perjeta/docetaxel arm.

"Treatment with Perjeta, Herceptin, and docetaxel chemotherapy significantly improved the rate of pCR by 58 percent compared to Herceptin and docetaxel alone," Genentech reported in a statement. The combination of Perjeta/Herceptin/docetaxel didn't increase adverse events or cardiac events in patients compared to those receiving Herceptin/docetaxel. The most common severe adverse events were neutropenia, febrile neutropenia, and diarrhea.

In TRYPHAENA, more than 225 patients with HER2-positive, early stage breast cancer were randomized to three neoadjuvant treatment arms: Perjeta; Herceptin and anthracycline-based chemotherapy followed by Perjeta; Herceptin, and docetaxel; anthracycline-based chemo followed by Perjeta, Herceptin, and docetaxel; and Perjeta, Herceptin, docetaxel, and carboplatin chemo.

The study was not powered to compare the three study arms. The primary endpoint was cardiac safety.

In the first arm, where patients received a Herceptin/Perjeta regimen with anthracycline-based chemo followed by Herceptin/Perjeta with docetaxel, pCR was around 62 percent. In the second arm, where anthracyclines were followed by the Perjeta/Herceptin/docetaxel combination, the pCR was 57 percent. In the third, anthracycline-free arm, pCR was 66 percent. No new cardiac adverse events were observed in any of the study arms, Genentech reported.

Having garnered priority review status for the sBLA, a decision from the agency is slated for Oct. 31, 2013.

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