F.D.A. Panel Backs Pre-Surgery Drug for Breast Cancer

A federal advisory committee cleared the way on Thursday for the first approval of a cancer drug that would be used to treat patients before surgery to remove their tumors.

The advisory committee to the Food and Drug Administration voted 13 to 0, with one abstention, that Perjeta, a Genentech drug approved last year for late-stage breast cancer, could also be used at the disease’s earliest stage.

Such pre-surgery treatment might help make some inoperable tumors amenable to surgery, or make tumors small enough to allow for breast-conserving surgery rather than complete removal of the breast.

Moreover, the approval could serve as a model for a new path to quicker approvals of cancer drugs.

“This is a historic moment,” Dr. Mikkael A. Sekeres, an associate professor at the Cleveland Clinic who served as the chairman of the advisory committee, said immediately after the vote. “We are supporting the rapid movement of a highly active drug for metastatic cancer to the first-line setting, with the hope that women with earlier stages of breast cancer will live longer and better.”

The F.D.A. still has to formally approve Perjeta for the new use but officials indicated it was likely to do so.

Perjeta, like the older Genentech drug Herceptin, is approved to treat only so-called HER2-positive tumors, which account for about 20 percent of all breast cancers. Pre-surgery treatment would be approved for only a minority of those patients, with large tumors or other features that increase the risk.

Genentech, which is part of the Swiss company Roche, estimates that 15,000 American women a year would be eligible for preoperative treatment with Perjeta, out of about 220,000 new cases of early-stage breast cancer.

Preoperative treatment, known as neoadjuvant therapy, is already fairly common for breast cancer and some other cancers, although the drugs are used off-label.

Approval of Perjeta — which would be the first neoadjuvant drug approval for any cancer, not just breast cancer — would presumably make it easier to obtain insurance reimbursement. It would also allow at least some women to gain access to Perjeta years earlier than they might otherwise.

Cancer drugs are typically tested first in patients with late-stage disease that has spread beyond the primary site. Because those patients are closer to dying than those with early disease, it takes less time to tell if a drug is improving survival. Also, side effects are less problematic for someone with little left to lose.

But metastatic breast cancer is virtually incurable. Bigger gains come from treating early-stage disease, typically after surgery, which is known as adjuvant therapy. In that use, drugs can prevent the return of the cancer, effectively curing the patient.

But it can take years to determine whether adjuvant therapy is preventing recurrences or prolonging lives. Herceptin was not approved for adjuvant use until eight years after it was approved for late-stage cancer. Data on the postsurgery use of Perjeta is not expected until 2016.

“Our current path to approval in early breast cancer is far too slow,” Dr. José Baselga, physician in chief at the Memorial Sloan-Kettering Cancer Center, said on behalf of Genentech at Thursday’s meeting in Silver Spring, Md.

So the F.D.A. issued a draft proposal last year that would allow pre-surgery treatment to be used as a basis for approval rather than postsurgery treatment.

Genentech’s main neoadjuvant trial involved only about 400 patients treated for a mere 12 weeks. About 39.3 percent of patients who received Perjeta plus Herceptin and taxotere had what was called a complete pathologic response, meaning no invasive cancer was detected in their breast tissue or in any removed lymph nodes. For patients who received only Herceptin and taxotere, only 21.5 percent had a complete pathologic response.

Despite their positive vote, some members of the advisory committee expressed concerns.

It is not clear whether a drug that increases the rate of pathologic complete responses will actually prolong lives or reduce recurrences. For that reason, the F.D.A. would give so-called accelerated approval to Perjeta, subject to confirmation with more data later.

Also, use of Perjeta did not increase the percentage of women in the trial who decided to switch from mastectomy to lumpectomy. There were concerns that Perjeta, which is known generically as pertuzumab, could raise the risk of damage to the heart.

Using Herceptin and Perjeta together for 9 to 18 weeks before surgery would cost $27,000 to $49,000, according to Genentech. And preoperative treatment would not eliminate the need for drugs after surgery.

By 
Published: September 12, 2013

The New York Times

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