Ribociclib Adds No pCR Benefit in Early HR+/HER2– Breast Cancer

The use of ribociclib plus endocrine treatment (ET) in patients with intermediate-risk hormone receptor-positive (HR-positive)/HER2-negative early breast cancer showed similar pathologic complete response (pCR) rates compared with standard-of-care chemotherapy in the neoadjuvant setting, according to the first results from the WSG ADAPTcycle clinical trial.

Researchers used the Oncotype DX recurrence score with early ET response (ET-R), measured by changes in the Ki-67 proliferation index (PI) after 2 to 4 weeks of endocrine therapy, to determine whether ribociclib could replace chemotherapy.

Nadia Harbeck, MD, PhD, Ludwig-Maximilian University, Munich, Germany, presented the phase 3 study findings during the 2025 European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress held in Munich, Germany.

Patients (n=1,682) were randomized based on nodal status, recurrence score, and ET-R (Ki-67 PI ≤10%) to receive neoadjuvant standard chemotherapy or ribociclib 600 mg/d plus an aromatase inhibitor with or without a gonadotropin-releasing hormone analog for 26 cycles. In the neoadjuvant setting, 554 patients were treated, and 497 were evaluable for pCR (n=314, ribociclib plus ET; n=183, chemotherapy).

Baseline characteristics were well balanced among study participants. In the ribociclib arm, the median age was 54 years and 48% were premenopausal; in the chemotherapy arm, the median age was 53 years and 50% were premenopausal. Tumors were cT2-4 (66% vs 68%), node positive (35% vs 39%), and central grade 3 (53% vs 49%), respectively. Moreover, the median recurrence score was 24 and the median Ki-67 PI was 25% in both arms.

The findings showed a slightly higher treatment burden in the ribociclib arm. Neoadjuvant treatment was stopped prematurely in 62 patients (19.7%) in the ribociclib arm—in 16.6% because of an adverse event (AE). In the chemotherapy arm, 26 patients (14.2%) stopped treatment, with 10.4% related to an AE.

Furthermore, 87 serious adverse drug reactions were reported in the ribociclib and chemotherapy arms (45 vs 42, respectively). The most common grade 3 AE was neutropenia (34.3% in the ribociclib arm and 13.3% in the chemotherapy arm).

In addition, the overall pCR rates were 5.7% in the ribociclib arm compared with 7.1% in the chemotherapy arm. In patients with cN0 status and those with cN1 status who had a recurrence score higher than 25 and ET-R, the pCR rates were 8.5% versus 9.4%, respectively. No pCR was observed in patients with cN2 or cN3 status. Nodal status was predictive of pCR, the researchers said.

The trial’s findings showed no significant pCR advantage of ribociclib plus ET over standard chemotherapy in patients with intermediate-risk HR-positive/HER2-negative early breast cancer. To determine whether ribociclib-based treatment should replace chemotherapy in the neoadjuvant setting, data for all randomized patients must be available, the researchers said.

Reference

Harbeck N, et al. 2025 ESMO Breast Cancer Annual Congress. Abstract No. 189O.