Where Does T-DM1 Fit In First-Line Treatment for HER2-Positive Breast Cancer?

In Clinical Trials by Barbara Jacoby

By: Dave Levitan

From: www.cancernetwork.com

Trastuzumab emtansine (T-DM1) with or without pertuzumab yielded good overall survival in patients with HER2-positive metastatic breast cancer according to the results of a phase III trial published in Cancer. Though these were not superior to survival seen with taxane-based therapy, T-DM1 should be considered an option for first-line therapy in patients deemed unsuitable for taxanes, according to researchers.

T-DM1, an antibody-drug conjugate designed to minimize toxicity, has been shown to be safe and effective in previously treated HER2-positive metastatic breast cancer, and encouraging results have been seen in the first-line setting. The phase III MARIANNE trial previously demonstrated that T-DM1 and T-DM1 plus pertuzumab were noninferior—though not superior—to trastuzumab plus a taxane (HT) in patients with previously untreated HER2-positive metastatic breast cancer.

The study included a total of 1,095 patients, all with HER2-positive breast cancer and no prior therapy for advanced disease. They were randomized to receive either HT (365 patients; 257 received trastuzumab plus docetaxel and 96 patients received trastuzumab plus paclitaxel), T-DM1 (367 patients), or T-DM1 plus pertuzumab (363 patients).

At the point of the final overall survival (OS) analysis, after a median follow-up duration of approximately 54 months, 512 patients had died in the trial. Of those, 169 were in the HT group, 175 were in the T-DM1 group, and 168 were in the T-DM1 plus pertuzumab group.

The median OS in the three groups was 50.9 months, 53.7 months, and 51.8 months, respectively. In comparison to the HT group, the hazard ratio (HR) for mortality for the T-DM1 group was 0.93 (97.5% CI, 0.731.20). For the T-DM1 plus pertuzumab group in comparison with the HT group, the HR was 0.86 (97.5% CI, 0.671.11). No subgroup examined showed any advantage for one treatment over another.

In the HT group, 67.9% of patients had a response; in the T-DM1 group, that rate was 59.7%, and in the T-DM1 plus pertuzumab group it was 64.2%. The median duration of response was numerically longer in the two T-DM1 groups than the HT group, and the median OS was numerically longer in patients with a tumor response within 6.5 months compared to those who did not have a response by that point.

More patients in the HT group had grade 3 or higher adverse events (55.8%) than those in the T-DM1 group (47.1%) or the combination therapy group (48.6%). Fewer patients in the T-DM1 groups discontinued any treatment due to adverse events (20.8% with T-DM1 and 23.0% with the combination) compared to the HT group (30.6%).

“The final analysis of MARIANNE supports the use of T-DM1 as a first-line treatment option for certain patients with HER2-positive metastatic breast cancer,” the authors concluded, adding that T-DM1 may be best suited for patients ineligible to receive taxane-based therapy.