SABCS Voice of China | Teams led by Professors Yuanting Gu and Jingruo Li Announce Results of CDK4/6 Inhibitor Combined with Letrozole as Neoadjuvant Treatment for Early or Locally Advanced HR+/HER2- Breast Cancer

The results of a single-arm, multicenter, prospective exploratory clinical study on the neoadjuvant treatment of HR-positive, HER2-negative (HR+/HER2-) breast cancer with Dalpiciclib combined with Letrozole, led by Professor Yuanting Gu and Professor Jingruo Li from the First Affiliated Hospital of Zhengzhou University, were selected for poster presentation at the 2023 SABCS conference. The unveiling of these results has attracted widespread attention. The study shows that for patients with early or locally advanced HR+/HER2- breast cancer, the objective response rate (ORR) of Dalpiciclib combined with Letrozole is 81%. Furthermore, an evaluation of the treatment’s effectiveness after 4 cycles holds potential as an optional scheme for neoadjuvant chemotherapy-free treatment. This publication has invited Professor Hong Zong from the First Affiliated Hospital of Zhengzhou University to provide a detailed introduction to this study.

Study Background

Dalpiciclib is a newly developed CDK4/6 inhibitor in China that targets and inhibits CDK4/6, key effector kinases that promote tumor cell growth. Its efficacy and safety in treating HR+ metastatic breast cancer have been affirmed. This study aimed to explore the efficacy and safety of Dalpiciclib combined with Letrozole as a neoadjuvant treatment for HR+/HER2- breast cancer.

Study Methods

This study employed a multicenter, single-arm, open design, enrolling early or locally advanced HR+/HER2- female breast cancer patients with an ECOG score of 0 to 1. Patients were first treated with four cycles of Dalpiciclib (150 mg po qd, d1-21, q4w) combined with Letrozole (2.5 mg po qd, q4w) as neoadjuvant treatment. Breast MRI was performed every two cycles. Based on the RECIST 1.1 criteria, patients with confirmed CR/PR after four cycles continued to receive four more cycles of Dalpiciclib combined with Letrozole. If the treatment was stable (SD) or the disease progressed (PD), the researcher would change to other treatment plans according to the actual situation of the participants. The primary study endpoint was the ratio of tumor residual burden (RCB0-I), and the secondary study endpoints included the ORR, the proportion of CCCA (C1D15 Ki67≤2.7%), and safety, among others.

Figure 1

Study Results

Between April 2022 and June 2023, 38 patients were enrolled in the study, all of whom had an ER (estrogen receptor) level of ≥50%. Among these patients, 84% (32/38) had a Ki67 index of ≥20%.

Table 1（1）

Table 1（2）

Of the patients, 21 completed the efficacy evaluation after 4 cycles, with an ORR of 81% (17/21). Twenty-two patients underwent a biopsy and Ki67 test on C1D15, among whom 55% (12/22) had a C1D15 Ki67 of ≤2.7%. 12patients underwent surgery after completing 8 cycles of neoadjuvant treatment with Dalpiciclib combined with Letrozole. The postoperative RCB scores were: 1 patient with RCB (0-I) and 11 patients with RCB (II-III).

Table 2

The most common adverse event was a reduction in neutrophil count, occurring in 66% (25/38) of patients. Of these, 16 patients (42%) experienced adverse events of grade 3 or higher, with no occurrences of grade 4 or higher adverse events.

Table 3

Study Conclusion

Dalpiciclib combined with Letrozole has shown promising tumor reduction and stage lowering effects for patients with early or locally advanced HR+/HER2- breast cancer. Patients with effective responses after 4 cycles of treatment have the potential to be considered for a chemotherapy-free neoadjuvant treatment option.

Researchers’ Comments

This study evaluated the efficacy and safety of Dalpiciclib combined with Letrozole as a chemotherapy-free neoadjuvant treatment option for patients with HR+/HER2- early or locally advanced breast cancer. The combination demonstrated good anti-tumor activity, with an ORR of 81% (17/21), and was well-tolerated. Additionally, 55% (12/22) of patients had a significant reduction in Ki-67 expression to ≤2.7% by C1D15. In summary, the neoadjuvant treatment of Dalpiciclib combined with Letrozole was well-tolerated and showed encouraging objective response rates in patients with HR+/HER2- early or locally advanced breast cancer. This chemotherapy-free neoadjuvant treatment option has the potential to become a viable option for this patient population, warranting further validation through large-scale clinical studies.