T-DM1 Regimens Equal Trastuzumab–Taxane For Metastatic Breast Cancer PFS

Trastuzumab emtansine alone or alongside pertuzumab matches trastuzumab plus taxane chemotherapy efficacy for the first-line treatment of metastatic breast cancer but with greater tolerability

medwireNews: MARIANNE trial results suggest that regimens based on the antibody–drug conjugate trastuzumab emtansine (T-DM1) offer comparable efficacy to trastuzumab plus taxane, but with fewer severe side effects for patients with treatment-naive, HER2-positive metastatic breast cancer (MBC).

“On the basis of the improved tolerability and noninferior PFS [progression-free survival] observed with T-DM1, it may provide an alternate treatment option to trastuzumab plus taxane in patients [with] HER2-positive MBC”, the investigators write in the Journal of Clinical Oncology.

“Indeed, the National Comprehensive Cancer Network has included T-DM1 in its breast cancer guidelines as a first-line treatment option for patients with HER2-positive MBC who are considered not suitable for treatment with the preferred regimen, pertuzumab, trastuzumab, and a taxane”, say Edith Perez, from Genentech in San Francisco, California, USA, and team.

The phase III trial included 1095 patients who were randomly assigned to receive T-DM1 with placebo, T-DM1 with pertuzumab, or trastuzumab plus taxane.

PFS achieved with T-DM1 plus placebo and T-DM1 plus pertuzumab were both noninferior but not superior to PFS with trastuzumab plus taxane, with median values of 14.1, 15.2 and 13.7 months, respectively.

Ongoing biomarker research may help explain why the predicted cytotoxic synergy for the T-DM1 plus HER2-targeted monoclonal antibody pertuzumab combination was not apparent, the researchers suggest.

Tumour response was also comparable for the T-DM1 plus placebo, T-DM1 plus pertuzumab and trastuzumab plus taxane treatment groups, with corresponding rates of 59.7%, 64.2% and 67.9%, although median response duration was longer in the two T-DM1 arms, at 20.7 and 21.2 months versus 12.5 months with trastuzumab plus taxane, the authors say.

“Further investigation is necessary to determine whether specific characteristics can define a subgroup of patients with a greater response to T-DM1 in this treatment setting”, they comment.

Grade 3 or more severe adverse events occurred at a nonsignificantly lower rate in the T-DM1 plus placebo and the T-DM1 plus pertuzumab groups than among the patients given trastuzumab plus taxane, at 45.4% and 46.2% versus 54.1%.

And this was reflected in a lower incidence of treatment discontinuation due to adverse events (18.3 and 19.1 vs 29.7%) and longer maintenance of health-related quality of life with T-DM1 plus placebo or pertuzumab than with trastuzumab plus taxane (7.7 and 9.0 vs 3.6 months).

Reference

Perez EA, Barrios C, Eiermann W, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2–positive, advanced breast cancer: Primary results from the phase III MARIANNE study. J Clin Oncol; Advance online publication 7 November 2016

DOI: 10.1200/JCO.2016.67.4887

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