Dr Tarantino on the Role of ADCs in HER2+ Breast Cancer

“T-DM1 led to a major shift in the way we think of targeting these tumors, because before T-DM1, there was no ADC approved for any solid tumors. [Data] from the EMILIA trial showed that compared [with] capecitabine and lapatinib T-DM1 improved progression-free survival, overall survival, and the tolerability profile. We realized that with magic bullets—with ADCs—we could improve outcomes and make chemotherapy more tolerable in some instances. This was a major shift.”

Paolo Tarantino, MD, a research fellow in Medicine at Dana-Farber Cancer Institute, detailed the role of antibody-drug conjugates (ADCs) in the HER2-positive breast cancer treatment paradigm and unmet needs that remain regarding ADCs for the treatment of patients with HER2-positive breast cancer.

Since the phase 3 EMILIA trial (NCT00829166), trastuzumab emtansine (T-DM1; Kadcyla) has contributed to a significant shift in the HER2-positive breast cancer treatment paradigm, especially during a time when ADCs were not yet approved for any solid tumors, Tarantino began. Of note, the study compared T-DM1 with capecitabine (Xeloda) plus lapatinib (Tykerb) for the treatment of patients with HER2-positive unresectable, locally advanced or metastatic breast cancer who were previously treated with trastuzumab (Herceptin) plus a taxane, he explained. Data from the study revealed that T-DM1 improved progression-free survival, overall survival (OS), and toxicity, he added. Specifically, the median OS was longer with T-DM1 at 29.9 months (95% CI, 26.3-34.1) compared with 25.9 months (95% CI, 22.7-28.3) in the capecitabine/lapatinib arm (HR, 0.75; 95% CI, 0.64-0.88). Crossover from the control arm to the T-DM1 arm was permitted; 136 of 496 patients made the switch after the second interim OS analysis.

Although there has been significant progress with ADCs for the treatment of patients with breast cancer, unmet needs remain, Tarantino noted. Particularly in the metastatic setting, where disease progression persists, identifying the right ADC at the correct time is key, he concluded.