Hans Wildiers, MD, PhD,
and colleagues presented results of the phase 3 TH3RESA study at the San Antonio Breast Cancer Symposium in December.
Results showed ado-trastuzumab emtansine (Kadcyla, Genentech), often referred to as T-DM1, significantly prolonged OS compared with treatment of physician’s choice among women with HER-2–positive metastatic breast cancer that progressed after treatment with two or more targeted therapies.
Antoinette R. Tan, MD, MHSc, FACP,
provided the following perspective on the findings.
Several phase 2 and phase 3 trials confirmed the efficacy and safety of ado-trastuzumab emtansine (Kadcyla, Genentech), often referred to as T-DM1, in patients with HER-2–positive metastatic breast cancer.
T-DM1 has been integrated into routine clinical practice since its approval in February 2013 based on the results of the phase 3 EMILIA trial, which demonstrated T-DM1 significantly improved PFS and OS compared with lapatinib (Tykerb, Novartis) and capecitabine in patients with HER-2–positive tumors previously treated with trastuzumab (Herceptin, Genentech) and a taxane.
After disease progression with a first-line taxane, trastuzumab and pertuzumab (Perjeta, Genentech)-based regimen, switching to T-DM1 is considered a standard approach in the second-line setting, and it is recommended in the recent ASCO clinical practice guideline on systemic therapy for advanced HER-2–positive breast cancer.
Results of the TH3RESA trial confirm that T-DM1 is more effective than traditional chemotherapy of physician’s choice and less toxic, confirming that T-DM1 can be used in patients with HER-2–positive metastatic breast cancer who have received multiple lines of therapy — third line and beyond — and after prior trastuzumab, taxane and lapatinib. Additionally, the safety profile remains favorable and consistent with prior studies, causing no alopecia, little neutropenia and modest thrombocytopenia.
The MARIANNE trial data, though, put an interesting twist on the placement of T-DM1 in the current treatment algorithm. In this study, T-DM1 was noninferior to trastuzumab and a taxane, and this has led the National Comprehensive Cancer Network to list T-DM1 as a possible first-line therapy in patients who are not suitable to be treated with the preferred first-line regimen of taxane, trastuzumab and pertuzumab, which demonstrated OS benefit.
In the future, treatment recommendations might need to be rewritten when the role of T-DM1 in the adjuvant and neoadjuvant settings is further defined from the results of the KAITLIN, KATHERINE and KRISTINE trials.
To date, it is clear that T-DM1 demonstrates survival benefit in previously treated patients with HER-2–positive metastatic breast cancer, with a favorable side effect profile compared with combinations of HER-2–targeted agents with chemotherapy.
Ellis PA, et al. Abstract 507. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Giordano SH, et al. J Clin Oncol. 2014;doi:10.1200/JCO.2013.54.0948.
Verma S, et al. N Engl J Med. 2012;doi:10.1056/NEJMoa1209124.
Wildiers H, et al. Abstract S5-05. Presented at: San Antonio Breast Cancer Symposium; Dec. 8-12, 2015; San Antonio.
For more information:
Antoinette R. Tan, MD, MHSc, FACP, is chief of breast medical oncology and co-director of the phase 1 program at Levine Cancer Institute at Carolinas HealthCare System in Charlotte, N.C. She also serves as a HemOnc Today Editorial Board member.
Disclosure: Tan reports research funding from Genentech/Roche paid to her institution.