By Toni Clarke
(Reuters) - Roche Holding AG's drug Perjeta, currently approved to treat metastatic breast cancer, should also be approved to help shrink tumors prior to surgery, an advisory panel of the U.S. Food and Drug Administration said on Thursday.
The panel voted 13 to 0, with one abstention, that the drug's benefits outweighed its risk, even though the trial to determine its safety and efficacy was small, with 107 patients taking Perjeta in combination with Roche's drug Herceptin and chemotherapy and 107 taking Herceptin plus chemotherapy alone.
Perjeta would be the first drug to be approved to shrink tumors prior to surgery in the United States. Dr. Mikkael Sekeres of the Cleveland Clinic and chairman of the advisory committee described the vote as historic. The FDA is not required to follow its panel's advice but typically does so.
The drug, also known as pertuzumab, is designed for patients whose tumors contain excess levels of the HER-2 protein. It was developed by Roche's Genentech unit. In the neoadjuvant, or pre-surgical setting, the hope is that it will shrink tumors and make them easier to remove.
Panelists concluded that the totality of the evidence, including the drug's relative safety in advanced breast cancer, tilted their decision in favor of approval despite the small trial size.
Much of the panel's discussion focused on the measure used to judge the trial's success - known as complete pathological response, or cPR. The FDA defines cPR as the absence of tumor tissue at the time of surgery, and Perjeta would be the first drug to be approved based on the measure.
There is no proof that if a patient achieves cPR she will live longer, or that her quality of life will improve. That makes it a relatively weak measure on which to base an approval.
Though more patients who took Perjeta had a cPR than did those who did not, it was unclear whether those patients would have had better outcomes anyway.
Roche based its application on recent FDA guidance allowing cPR to be used to support accelerated approval, under which a drug may be approved based on incomplete data pending additional trials.
As required by the FDA, the company is conducting a follow-up trial using 4,800 patients who have already had surgery.
Still, the FDA made clear that it considered the Perjeta case unique in that the drug is already used and has a track record. Most drugs will not be approved based on such limited data.
Panelists urged the FDA to carefully scrutinize the results of the follow-up trial to ensure they support the benefit to patients suggested by the small trial.
In 2011, the FDA withdrew approval of Genentech's drug Avastin after deciding it was not safe or effective in breast cancer.
Avastin is approved to treat certain types of colon, lung, kidney and brain cancer. It was approved under the accelerated program for breast cancer in 2008. Subsequent trials showed only a small effect on tumor growth with no evidence that patients lived longer than those taking standard chemotherapy.
The Perjeta regimen would be given as part of a broad treatment program that would include the chemotherapies docetaxel and either fluorouracil, epirubicin, and cyclophosphamide or carboplatin.
The FDA has expressed some concern that Perjeta, in combination with anthracycline chemotherapies such as epirubicin, could cause heart problems. Roche said it intends to address the questions with an additional trial of Perjeta in combination with a variety of chemotherapy regimes, including anthracyclines.
(Reporting by Toni Clarke in Washington; Editing by Maureen Bavdek and Jim Marshall)