March 2016, Vol. 5, No. 2

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Benefit for T-DM1 Confirmed

San Antonio Breast Cancer Symposium

The antibody-drug conjugate trastuzumab emtansine (T-DM1) improved overall survival (OS) compared with physician’s choice of therapy for patients with pretreated HER2-positive metastatic breast cancer, according to final results from the phase 3 TH3RESA trial. The study was supported by Roche.

Treatment with T-DM1 led to a clinically meaningful and statistically significant improvement in OS compared with physician’s choice of therapy (control arm, P = .0007), reflecting a relative improvement of 32%. The absolute difference in survival in these patients who progressed on prior HER2-directed therapy (trastuzu­mab, taxane, and lapatinib) was 6.9 months: median OS of 22.7 months for T-DM1 versus 15.8 months with physician’s choice of therapy.

“This excellent survival benefit was achieved in the T-DM1 arm despite the fact that more than 50% of patients in the physician’s choice of therapy arm crossed over to T-DM1, and about 80% of patients in the control arm had received trastuzumab-containing regimens. These findings solidify the role of T-DM1 in patients with previously treated metastatic breast cancer,” stated lead author Hans Wildiers, MD, PhD, University Hospitals Leuven, Belgium.

T-DM1 is approved by the FDA for the treatment of metastatic breast cancer based on results from the EMILIA trial, which included less advanced disease. TH3RESA randomized 602 patients to T-DM1 or physician’s choice of therapy and allowed crossover to T-DM1 at disease progression, Wildiers explained.

At the first interim analysis of TH3RESA, T-DM1 doubled progression-free survival from 3.1 months with physician’s choice of therapy to 6.2 months. At that time, a trend toward improved survival was seen for T-DM1, but it was too early to evaluate OS.

The final analysis of OS showed that at a median follow-up of 30.5 months, OS crossed the stopping boundary, he said.

At baseline, patients were very sick: 50% of patients had estrogen receptor–positive tumors, 75% had visceral involvement, more than 50% had brain metastases, and about 10% of these patients had to be stabilized prior to initiating study treatment.

Within the study, 49% of the control arm crossed over to T-DM1 at disease progression, and another 6% crossed over as a nonstudy treatment. Patients were treated until disease progression.

Nonhematologic toxicity was reported more frequently with physician’s choice of therapy, with more diarrhea, neutropenia, and febrile neutropenia. Thrombocytopenia was more frequent in the T-DM1 arm. The incidence of grade ≥3 adverse events was higher in the control arm: 47.3% compared with 40% in the T-DM1 arm.

As of data cutoff in February 2015, about 25% of patients in the trial were still being treated with T-DM1 and had not yet progressed. “There are some long-term survivors,” Wildiers said.


C. Kent Osborne, MD, moderator of the press conference where these data were presented, said that now that there is a biomarker for treatment for HER2-positive breast cancer, and there are treatments targeted to this biomarker, “It turns out that HER2-positive breast cancer is a good tumor to have.”

“This study raises an interesting question of how long to keep patients on the drug if they are in complete remission. This also raises the issue of cost and the question of who to treat,” Osborne continued. “Luckily the biomarker shows us who to treat.”

Osborne is Director of the Dan L. Duncan Comprehensive Cancer Center at the Baylor College of Medicine in Houston, TX.

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