Trial Results Support Frontline Use of T-DM1 in HER2‐Positive Metastatic Breast Cancer


Treatment with trastuzumab emtansine demonstrated similar overall survival across 3 treatment arms of patients with HER2‐positive metastatic breast cancer.

Treatment with trastuzumab emtansine (T‐DM1; Kadcyla) demonstrated similar overall survival (OS) across 3 treatment arms, with each resulting in a median OS longer than 50 months, among patients with HER2‐positive metastatic breast cancer, according to the final analysis of the phase 3 MARIANNE trial. 

“These results support T‐DM1 as a first‐line treatment for patients with HER2‐positive metastatic breast cancer who are deemed unsuitable for taxane‐based therapy,” the researchers wrote.

The randomized phase 3 trial evaluated the safety and efficacy of T‐DM1 plus a placebo and T‐DM1 plus pertuzumab (Perjeta) for the treatment of patients with HER2‐positive, progressive or recurrent locally advanced breast cancer who had not received prior chemotherapy for their metastatic disease versus the standard of care.

Progression‐free survival (PFS) served as the primary endpoint, for which T‐DM1 with (median PFS, 15.2 months) or without (median PFS, 14.1 months) pertuzumab showed noninferior PFS, but not superior to standard of care (median PFS, 13.7 months) and better tolerability than trastuzumab plus a taxane. In addition, T‐DM1–treated patients maintained baseline health‐related quality of life longer than their counterparts who received standard of care.

 In the final analysis, the researchers reported the OS analysis from 1,095 patients, as well as updated safety data, and additional patient‐reported outcomes and biomarker analyses.

The median OS was similar across treatment arms: 50.9 months in the standard of care arm, 53.7 months in the T‐DM1 group, and 51.8 months for those who received T‐DM1 plus pertuzumab.

Among patients with an objective tumor response, OS was longer with T‐DM1 (64.4 months) and T‐DM1 plus pertuzumab (not reached), compared with standard of care (56.3 months).

The updated safety profiles of T‐DM1 and pertuzumab were generally consistent with the primary analysis.

The incidence of grade 3 or higher adverse events (AEs) was greater with standard of care (55.8%), compared with T‐DM1 (47.1%) or T‐DM1 in combination with pertuzumab (48.6%). The most commonly reported grade 3 or higher AEs in the T‐DM1 arm were thrombocytopenia, transaminase elevations, and anemia, whereas neutropenia, febrile neutropenia, and diarrhea were the most common in the standard of care arm. 

Median time to clinically meaningful deterioration in neurotoxicity symptoms was shorter with standard of care (2.1 months) and the T‐DM1-pertuzumab combination (4.2 months) than with T‐DM1 (6.2 months).

“Although the control arm has since been superseded by trastuzumab, taxane, and pertuzumab in the first‐line setting, the results of MARIANNE nonetheless demonstrate that single‐agent T‐DM1 has a favorable tolerability profile in comparison with (standard of care), including a lower incidence of grade 3 or higher neutropenia, febrile neutropenia, and diarrhea,” the researchers wrote, adding that fewer patients on T‐DM1 were bothered from treatment-related AEs in comparison with the other arms.

“…They also reported a lower incidence of alopecia and a nearly 3‐fold increase in the time to patient‐experienced increases in neurotoxicity symptoms,” the researchers concluded. “These data provide further support for clinical practice guidelines that recommend first‐line T‐DM1 as an appropriate choice for patients deemed unsuitable for taxane‐based therapy.”



Perez EA, Barrios C, Eiermann W, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2–positive advanced breast cancer: Final results from MARIANNE. Cancer. doi:10.1002/cncr.32392.

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