The FDA granted a broader label to Herceptin (trastuzumab), paving the way for Genentech Inc. to promote its most visible targeted oncology product as a front-line treatment for breast cancer.
Specifically, the new indication allows for the use of Herceptin in a treatment regimen containing doxorubicin, cyclophosphamide and paclitaxel (Taxol, Bristol-Myers Squibb Co.) for the adjuvant treatment of HER2-positive, node-positive breast cancer. Calling the approval "one of the most important things to happen" in this setting in more than 25 years, Pamela Klein, the company's vice president of clinical oncology, said it signals a beneficial change in treating localized, early stage breast cancer. That's because of the drug's positive impact on the aggressive form of the disease, which otherwise causes a "poor prognosis" for women diagnosed with it, according to a statement from the FDA's Steven Galson, the director of its Center for Drug Evaluation and Research.
Adding Herceptin to standard adjuvant treatment cuts the risk of recurrence and metastasis in half, stretching survival for years rather than months because the early intervention means fewer patients will die. Nearly 213,000 new breast cancer cases are diagnosed in the U.S. each year, coupled with about 41,000 annual related deaths.
"It's metastatic disease that kills," Klein, a breast cancer oncologist by training, told BioWorld Today. "This is one of the first times that we've been able to take a targeted drug into early stage disease, and this is where we're going to see the biggest impact on patients' lives."
Standard treatment for early stage breast cancer begins with surgery for local tumor removal, followed by radiation and chemotherapy that often includes an anthracycline, a taxane and anti-estrogen therapy if they're estrogen receptor (ER)-positive. Adding the humanized antibody to that regimen lowered the risk of recurrence by 52 percent in women with HER2-positive breast cancer, compared to those patients who received standard adjuvant therapy alone. In addition, after three and a half years, 87 percent of women treated with Herceptin plus chemotherapy were disease-free compared to 71 percent of those on chemotherapy alone.
Also, the Herceptin-chemotherapy regimen improved overall survival, according to an analysis conducted after patients had been followed for a median of 24 months, reducing the risk of death by 33 percent. That's equivalent to a 49 percent improvement in overall survival.
The data come from an interim joint prospective analysis of two large, Phase III adjuvant studies in more than 3,500 patients, one conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and North Central Cancer Treatment Group (NCCTG). Patients in both studies initially received doxorubicin and cyclophosphamide, followed by 12 weeks of paclitaxel and 52 weekly infusions of Herceptin. Dosing of the latter two began at the same time.
On the basis of those studies, South San Francisco-based Genentech submitted a supplemental biologics license application earlier this year. The data also supported Herceptin's off-label use in the front-line setting, and while the company can't yet quantify that practice relative to overall sales that totaled $302 million in the U.S. last quarter, clearly the FDA's "formal" consent has the potential to boost revenues even more. That was the message in a research note published by Adam Walsh, an analyst with Jeffries & Co. Inc. in San Francisco.
The approval ensures better access through reimbursement - present use in the adjuvant setting "appears moderately constrained" by reimbursement, Walsh wrote - and gives the company's sales force the freedom to promote the data. He pointed to a survey of oncologists who foresee increased penetration in adjuvant breast cancer patients, estimating Herceptin use to ramp from 22.6 percent penetration in the first quarter of this year to 33.2 percent in 2010. Walsh predicted full-year sales of $2 billion next year, $2.4 billion in 2008, $2.8 billion in 2009 and $3.2 billion in 2010.
An additional factor in sales growth is the potentially longer duration of use than in the metastatic setting, which would yield higher sales numbers even though the monthly drug cost would remain constant across adjuvant and metastatic use. However, it's not yet clear whether longer use is beneficial, Klein said.
That could be answered by an additional trial under way to support another filing, the Herceptin Adjuvant (HERA) study. In addition to a control group, the three-arm European trial also is comparing one or two year's worth of Herceptin in the other arms to determine the benefit of longer therapy. Data from the two-year group won't be available until 2008.
A fourth adjuvant trial, the Breast Cancer International Research Group (BCIRG) study, has looked at Herceptin as part of a different regime containing Taxotere and carboplatin, absent an anthracycline, in addition to the now-approved regimen and a control arm. Data from both Herceptin arms were better than the control arm and significantly reduced the risk of recurrence.
"We now have had four global trials that have all shown a very consistent benefit with Herceptin when used in early stage breast cancer," Klein said, noting that the last two studies enrolled a larger number of more high-risk, lymph node-negative patients than the NSABP and NCCTG trials.
Genentech is preparing an FDA filing for Herceptin in combination with Taxotere for patients with first-line, metastatic, HER2-positive breast cancer, and is discussing a submission with the FDA on the HERA and BCIRG studies in early stage, HER2-positive breast cancer.
Herceptin first received FDA approval eight years ago to specifically target HER2-positive breast cancer, which accounts for about a quarter of all cases. It was cleared for two uses: in combination with paclitaxel for metastatic breast cancer patients whose tumors overexpress the HER2 protein and who have not received chemotherapy for their metastatic disease, and as a single agent for metastatic breast cancer patients whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens for their metastatic disease.
Because of Herceptin's link to serious or life-threatening cardiac events, patients must be screened for heart function before beginning and during treatment with the drug.
On Friday, Genentech's stock (NYSE:DNA) gained $1.15 to close at $81.87.