Dr Tarantino on Trials Reshaping the Perioperative Treatment Algorithm for HER2+ Breast Cancer

[A] major change that occurred after the first presentation and publication of [the] KATHERINE [data was] that it suddenly became mandatory for all patients with stage II to III HER2-positive breast cancer to receive neoadjuvant treatment, because [the data] showed that if you select those patients [who] have more aggressive or resistant disease, [if] you escalate their treatment after surgery, [that] can affect outcomes later."

Paolo Tarantino, MD, a breast medical oncologist at Dana-Farber Cancer Institute and researcher at the University of Milan, discussed the clinical impact of the phase 3 KATHERINE trial (NCT01772472) in reshaping the perioperative treatment algorithm for patients with HER2-positive early-stage breast cancer with residual disease after neoadjuvant therapy.

The publication of KATHERINE marked a major turning point in the management of HER2-positive stage II and III breast cancer, Tarantino noted. This study included patients with Findings from the study demonstrated that patients with HER2-positive early breast cancer who had residual disease following neoadjuvant treatment with a taxane and trastuzumab (Herceptin), followed by surgery. In the adjuvant setting, patients treated with ado-trastuzumab emtansine (Kadcyla; T-DM1) experienced a 3-year invasive disease-free survival (IDFS) rate of 88.3% vs 77.0% in those treated with trastuzumab (HR, 0.50; 95% CI, 0.39-0.64; P < .001).

This evidence led to widespread adoption of neoadjuvant therapy as the standard approach for all patients with stage II or III HER2-positive disease, Tarantino explained, noting that a similar strategy has been adopted for patients with triple-negative disease. According to Tarantino, identifying residual disease and tailoring adjuvant therapy based on this biologic response has helped mitigate poor prognostic indicators and provided a foundation for more individualized treatment escalation.

In addition to reinforcing the utility of T-DM1 in the adjuvant setting, the KATHERINE trial also prompted the exploration of potentially more effective agents in the perioperative setting. Tarantino highlighted the ongoing phase 3 DESTINY-Breast05 trial (NCT04622319), which is evaluating whether fam-trastuzumab deruxtecan-nxki (Enhertu) may offer superior efficacy compared with T-DM1 in this high-risk, post-surgical population.

Although T-DM1 remains the current adjuvant standard for patients with residual HER2-positive disease, Tarantino emphasized that the principles outlined by KATHERINE have had broader implications. The trial’s findings underscored the importance of response-guided treatment and supported the continued investigation of novel antibody-drug conjugates and therapeutic combinations to further improve survival outcomes in early-stage HER2-positive breast cancer, he concluded.