On December 19, 2014 Roche reported top-line results of the Phase III MARIANNE study (Press release Hoffmann-La Roche, DEC 19, 2014, View Source [SID:1234501215]). The study evaluated three HER2-targeted regimens – Kadcyla (trastuzumab emtansine) plus Perjeta (pertuzumab), Kadcyla alone, and Herceptin (trastuzumab) plus taxane chemotherapy – in people with previously untreated (first line) advanced HER2-positive breast cancer. The study showed the three regimens helped people live without their disease worsening (PFS) for a similar amount of time, meeting its non-inferiority endpoint as assessed by an Independent Review Committee (IRC). However, neither Kadcyla-containing treatment arm significantly improved PFS compared to Herceptin and chemotherapy. Adverse events observed in the two experimental arms of the study were generally consistent with those seen in previous studies of Kadcyla and/or Perjeta.

In their approved uses for advanced HER2-positive breast cancer, Kadcyla and Perjeta have been shown to extend survival. Kadcyla is approved for people with previously treated disease (second and later lines). Perjeta is approved in combination with Herceptin and chemotherapy for people with previously untreated disease (first line).

“Over the past 30 years, we have made significant progress in treating one of the most aggressive forms of advanced breast cancer with medicines that extend patients’ lives across the course of their disease. In this study, we had hoped to show improvement in progression-free survival without the use of traditional chemotherapy in the first line treatment of patients with advanced HER2-positive breast cancer,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “While MARIANNE didn’t achieve this result, we will continue to study these medicines, as well as investigational treatments for other types of breast cancer, with the goal of improving outcomes for patients.”

Data from the MARIANNE study will be presented at an upcoming medical meeting. Roche will discuss the data with health authorities.

About the MARIANNE Study

The Phase III MARIANNE study (NCT01120184; BO22589) is an international, randomized, multicenter, three-arm study involving 1,095 people with HER2-positive advanced breast cancer – either with inoperable locally advanced disease that had worsened during or returned after previous treatment, or with disease that had spread to other areas of the body.2 People with advanced breast cancer at diagnosis and people whose disease had worsened following either neoadjuvant or adjuvant treatment were eligible.

People enrolled in the study received treatment with either:

A combination of Kadcyla and Perjeta
Kadcyla alone, or
Herceptin and either docetaxel or paclitaxel chemotherapy.

The primary endpoint of the MARIANNE study is PFS as assessed by an Independent Review Committee (IRC). Secondary endpoints include overall survival, response rate, and the incidence of adverse events. Differences in these endpoints were assessed in each of the Kadcyla-containing treatment arms compared to the Herceptin plus chemotherapy arm, and also between the two Kadcyla-containing arms.