Dr Tarantino on Frontline Treatment Considerations in Metastatic HER2+ Breast Cancer

"We still use the same treatment strategy developed [in the CLEOPATRA trial] a decade ago, but we made this better, and we do expect further improve this [standard] with upcoming trials."

Paolo Tarantino, MD, a breast medical oncologist at Dana-Farber Cancer Institute and researcher at the University of Milan, discussed considerations around the frontline treatment of metastatic HER2-positive breast cancer and how evolving data have refined treatment approaches over the past decade.

The phase 3 CLEOPATRA trial (NCT00567190), conducted over 10 years ago, established the combination of trastuzumab (Herceptin), pertuzumab (Perjeta), and docetaxel (THP) as a standard of care in the frontline setting. Findings from the study showed THP generated a median progression-free survival (PFS) of 18.5 months compared with 12.4 months for placebo plus trastuzumab and docetaxel. In the final analysis of the study, the median overall survival was 56.5 months (95% CI, 49.3-not reached) in the THP arm vs 40.8 months (95% CI, 35.8-48.3) in the control arm.

Although THP has remained the standard of care in the frontline setting since the emergence of these data, Tarantino noted that, despite the durability of this regimen, several key studies have since helped tailor its components to better meet individual patient needs.

Findings from the phase 3 PERUSE study (NCT01572038) indicated that paclitaxel and nab-paclitaxel (Abraxane) may be substituted for docetaxel without compromising efficacy, offering improved tolerability. Tarantino also emphasized the role of endocrine therapy in patients with hormone receptor (HR)–positive, HER2-positive disease. Data supporting the combination of HER2 blockade with agents such as aromatase inhibitors have expanded treatment options for select patients, especially those with indolent disease or chemotherapy contraindications.

The most notable recent advancement, according to Tarantino, is the incorporation of CDK4/6 inhibitors into the maintenance setting for those with HR-positive, HER2-positive disease. The phase 3 AFT-38 PATINA trial (NCT02947685) demonstrated that adding palbociclib (Ibrance) to endocrine therapy and continued HER2 blockade extended PFS in patients with triple-positive disease who had completed induction chemotherapy. This strategy represents a meaningful evolution of the CLEOPATRA framework, particularly for patients eligible for long-term maintenance therapy.

Tarantino underscored that although THP remains the backbone of first-line therapy, contemporary practice allows for its customization based on patient characteristics and treatment goals. In some cases, THP may be paired with alternative chemotherapy backbones or endocrine therapy, with or without CDK4/6 inhibition.