番茄社区

CHICAGO -- Neoadjuvant therapy with an investigational biosimilar drug for trastuzumab (Herceptin) yielded equivalent results to the original drug in women with early-stage HER2-positive breast cancer, researchers reported.

In a phase III clinical trial, the biosimilar agent, dubbed CT-P6, yielded pathological complete responses in 46.8% of participants, according to Justin Stebbing, MD, of Imperial College Healthcare NHS Trust in London, and colleagues.

Treatment with trastuzumab itself led to complete responses in 50.4% of patients, a difference that was within a pre-set equivalence margin, Stebbing and colleagues reported at the and .

Both drugs were delivered in combination with standard chemotherapy with docetaxel, followed by fluorouracil, epirubicin, and cyclophosphamide (FEC).

CT-P6 is the second trastuzumab biosimilar to be presented at an ASCO meeting. Last year, investigators reported on Myl-1401O in combination with a taxane drug to treat women with HER2-positive metastatic breast cancer. That study showed the novel substance had similar efficacy and safety to the original trastuzumab, the researchers said at the time.

The main thing driving the development of biosimilar drugs is economics, according to ASCO President Daniel Hayes, MD, who is also a breast cancer specialist at the University of Michigan in Ann Arbor.

He told 番茄社区 that trastuzumab was "one of the great game-changers" in breast cancer therapy, but there's a desire to lower the cost of treatment and thereby widen access to the drug.

Indeed, Stebbing and colleagues noted that a course of brand-name trastuzumab can cost as much as $70,000.

But for clinicians, Hayes said, the key question will be whether the copycat drugs work as well as the original.

"How biosimilar does a biosimilar have to be?" he asked. In the case of trastuzumab, Hayes argued, it will have to be "as good or better than Herceptin and not just in response rates or even progression-free survival, but in overall survival."

Lisa Carey, MD, a breast oncologist at UNC Lineberger Comprehensive Cancer Center in Chapel Hill, NC, noted that the production of biosimilar drugs is not the same as producing generic drug molecules.

As protein-based biologic agents, their manufacturing process is more complicated and their precise structures may differ in certain ways.

"It wouldn't surprise me to see some batch effects," she told 番茄社区. "There is some concern about unmeasured variability that will come out later that will be different from the original drug."

But the new drugs have to go through regulatory hoops that should "minimize" that risk, she told 番茄社区.

Stebbing and colleagues enrolled 549 women with stages 1 through IIIa operable breast cancer and randomly assigned them to neoadjuvant therapy with CT-P6 or trastuzumab for eight three-week cycles.

The biologic drugs were accompanied by docetaxel for the first four cycles and the standard FEC chemotherapy regimen for the last four.

To be eligible, women had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, left ventricular ejection fraction of at least 55%, adequate function of liver, kidney, and bone marrow, with at least one measureable lesion and known estrogen and progesterone receptor status.

They were excluded if they had bilateral disease, previous breast cancer therapy, previous anthracycline exposure, or were pregnant or breast-feeding.

Clinical equivalence was defined as falling within a 15% margin -- the 95% confidence interval of the treatment difference had to be contained with an interval from minus 0.15 to 0.15.

The per protocol population included 248 patients in the CT-P6 arm and 256 in the trastuzumab arm.

Pathological complete response rates were similar between the arms and the treatment outcome difference was estimated to be minus 0.04% (95% CI -0.12 to 0.5).

The drugs also had similar safety, Stebbing and colleagues reported: 7% of patients getting CT-P6 reported serious treatment-emergent adverse events, compared with 8% of those getting trastuzumab.

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