September 09, 2013
2 min read

Expanded access study confirms Kadcyla safe, active in pretreated HER-2–positive breast cancer

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Ado-trastuzumab emtansine appeared safe and effective in previously treated patients with HER-2–positive locally advanced or metastatic breast cancer, according to results of an expanded access study presented at the Breast Cancer Symposium.

The multicenter T-PAS study more closely resembled clinical practice than prior investigations into the drug, according to Denise A. Yardley, MD, of Sarah Cannon Research Institute in Nashville, Tenn., and colleagues.


Denise A. Yardley

Ado-trastuzumab emtansine (Kadcyla, Genentech), formerly known as T-DM1, is an antibody drug conjugate that incorporates antitumor activities of trastuzumab (Herceptin, Genentech) with the potent cytoxic agent emtansine.

The 215 patients in the T-PAS study had undergone a median seven prior treatments (range, 1-23). Eligibility included prior anthracycline and taxane treatment, prior capecitabine (Xeloda, Hoffmann-La Roche) or fluorouracil treatment, and therapy with at least two HER-2–targeting agents, including trastuzumab and lapatinib (Tykerb, GlaxoSmithKline). The median cumulative dose of anthracycline was 240 mg/m2 (range, 6-2,645).

At baseline, the median rate of left ventricular ejection fraction was 60%, and half of patients had cardiovascular disease.

Patients received 3.6 mg/kg ado-trastuzumab emtansine every 3 weeks. The median duration of treatment was 5 months (range, 0-23), and 15.8% of patients received 18 or more cycles.

Safety served as the primary endpoint and was assessed on the first day of each cycle. Objective response rate in patients with measurable disease served as the secondary endpoint.

Median follow-up was 5.9 months (range, 0.1-25.3).

Researchers reported an overall objective response rate of 25.6%.

The most common adverse events were fatigue (50.7%), nausea (36.3%) and headache (24.2%).

Researchers indicated 43.7% of patients experienced grade ≥3 adverse events, the most common of which were thrombocytopenia (7.9%), fatigue (4.7%), increased aspartate aminotransferase (3.7%) and anemia (3.7%).

The rate of serious adverse events was 18.1%, but no grade ≥3 bleeding events occurred.

Cardiac dysfunction — primarily from asymptomatic decreases in left ventricular ejection fraction — occurred in eight patients; four of them were grade ≥3. Three patients discontinued treatment due to cardiac dysfunction.

“In this study that more closely reflects the real-world setting, the safety profile of [ado-trastuzumab emtansine] was similar to that previously reported in conventional clinical trials, with no new safety signals,” Yardley and colleagues wrote. “In this pretreated population, significant activity was observed.”

Disclosure: The researchers report consultant or advisory roles with, research funding and honoraria from, employment or leadership positions with, and stock ownership in Genentech/Roche.

For more information:

Yardley DA. Abstract #166. Presented at: Breast Cancer Symposium; Sept. 7-9, 2013; San Francisco.