Recent studies published in the Journal of Clinical Oncology highlight advancements in the treatment of HER2-positive advanced or metastatic breast cancer. These trials explore novel therapeutic strategies, including antibody-drug conjugates and combination regimens, to improve outcomes for patients with this aggressive form of the disease.
Trastuzumab Duocarmazine (T-Duo) in Pretreated HER2-Positive Metastatic Breast Cancer
The phase III TULIP trial evaluated the efficacy of trastuzumab duocarmazine (T-Duo), a third-generation HER2-targeted antibody-drug conjugate, in patients with previously treated advanced or metastatic HER2-positive breast cancer. The study, led by Turner et al., randomized 437 patients to receive either T-Duo or physician's choice (PC) of treatment after disease progression on or after at least two HER2-targeted therapies or ado-trastuzumab emtansine (T-DM1).
The results demonstrated a statistically significant improvement in progression-free survival with T-Duo compared to PC. Median progression-free survival was 7.0 months in the T-Duo group versus 4.9 months in the PC group (HR = 0.64, 95% CI = 0.49–0.84, P = .002). While the initial analysis did not show a statistically significant difference in overall survival (20.4 months vs 16.3 months, HR = 0.83, P = .153), the study suggests a potential benefit in heavily pretreated patients.
However, T-Duo was associated with significant ocular toxicity, leading to treatment discontinuation in a notable proportion of patients. Grade ≥ 3 adverse events were more frequent in the T-Duo group (52.8%) compared to the PC group (48.2%), with keratitis and conjunctivitis being the most common. Ocular toxicity led to treatment discontinuation in 20.8% of patients receiving T-Duo.
Eribulin Plus Trastuzumab/Pertuzumab (HP) as First-Line Treatment
The EMERALD trial, a Japanese phase III noninferiority study, investigated the addition of eribulin to trastuzumab/pertuzumab (HP) as a first-line treatment for HER2-positive, locally advanced or metastatic breast cancer. Yamashita et al. randomly assigned 446 patients to receive HP with either eribulin or a taxane (docetaxel or paclitaxel).
The study met its primary endpoint, demonstrating that HP plus eribulin was noninferior to HP plus a taxane in terms of progression-free survival. Median progression-free survival was 14.0 months in the eribulin group versus 12.9 months in the taxane group (HR = 0.95, 95% CI = 0.76–1.19). Median overall survival was not reached in the eribulin group versus 65.3 months in the taxane group (HR = 1.09, 95% CI = 0.76–1.58).
Treatment-related grade ≥ 3 adverse events were similar in both groups, with neutropenia being the most common in both arms.
Pertuzumab Retreatment in HER2-Positive Advanced/Metastatic Breast Cancer
The PRECIOUS study, a Japanese phase III trial, evaluated the efficacy of pertuzumab retreatment in patients with HER2-positive locally advanced/metastatic breast cancer who had previously received pertuzumab-containing regimens. Yamamoto et al. randomly assigned 219 patients to receive trastuzumab plus physician’s choice of chemotherapy (PTC) with or without pertuzumab.
The final overall survival analysis showed a significant benefit with the addition of pertuzumab retreatment to trastuzumab plus chemotherapy. Median overall survival was 36.2 months in the PTC group versus 26.5 months in the TC group (HR = 0.73, 95% CI = 0.55–0.97).
