244P - Efficacy and safety of dalpiciclib, exemestane, and goserelin as neoadjuvant therapy in premenopausal HR-positive, HER2-negative breast cancer patients: A phase II clinical trial

Background

Neoadjuvant chemotherapy is a standard approach for treating locally advanced HR-positive, HER2-negative breast cancer (BC) in premenopausal women, despite its lower efficacy in this subgroup. The integration of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy has markedly improved outcomes in metastatic settings, suggesting potential benefits in neoadjuvant applications. This study aims to evaluate the feasibility and efficacy of transitioning premenopausal patients who are unresponsive to initial chemotherapy to neoadjuvant endocrine therapy (NET) incorporating CDK4/6i.

Methods

This multicenter, randomized, non-controlled, Simon's two-stage trial enrolled premenopausal women with stage II-III HR-positive, HER2-negative BC. Participants initially received two cycles of TAC (docetaxel, doxorubicin, and cyclophosphamide). Those with stable disease (SD) were randomized 1:1 to receive either 16 weeks of dalpiciclib, exemestane, and goserelin or four additional cycles of TAC. The primary endpoint was the objective response rate (ORR) in the experimental group, with secondary endpoints including residual cancer burden, preoperative endocrine prognostic index, event-free survival, and safety.

Results

From April 11, 2023, to April 9, 2024, 49 patients were screened, with 40 completing two cycles of TAC. Of these, 32 exhibiting SD were randomized. The neoadjuvant endocrine group (n=15) demonstrated an ORR of 63.7% (7/11), surpassing the desired ORR target of 40%. The chemotherapy group (n=17) showed an ORR of 50.0% (7/14). Adverse events, including neutropenia, leukopenia, and night sweats, were manageable. Patient-reported outcomes indicated an improved quality of life with NET.

Conclusions

Preliminary results advocate for the use of dalpiciclib, exemestane, and goserelin as an effective alternative to continued chemotherapy in premenopausal HR-positive, HER2-negative BC patients unresponsive to initial neoadjuvant chemotherapy. This strategy offers notable treatment benefits, diminishes adverse events, and enhances patient quality of life. Further enrollment up to 43 participants will continue based on these findings.

Clinical trial identification

NCT06009627.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.