2022 ESMO | Professor Zhang Qingyuan: Darcille combined with AI front-line treatment HR+/HER2-advanced breast cancer debut, the effect is amazing

*For medical professionals for reading reference

DAWNA-2 research mid-term analysis data is freshly released.

The annual European Cancer Internal Science Association (ESMO) conference arrived on schedule, from September 9th to 13th, 2022 (Central Europe and summer) was held in Paris, France, and gathered experts and scholars in the global tumor field. Share the latest research progress and explore future exploration directions. At this conference, DAWNA-2 studied by Professor Zhang Qingyuan, a Cancer Hospital of Harbin Medical University as one of the PI, was selected as "Proffered Paper" special session (LBA16). Singing the international stage. DAWNA-2 Studies are a multi-center, random, control, phase III clinical trial, and evaluate the value of Darcilla's combined aromatase inhibitors (AI: Cadozozool or Anenzozole). [1]. The interim analysis released by this conference shows that the mid-level no progressive survival (PFS) of the Darcilla's joint group exceeded 30 months. It is the current CDK4/6 inhibitor combined with AI first-line treatment HR+/HER2-advanced breast cancer. PFS is expected to become a preferred plan for HR+/HER2-advanced breast cancer. Cancer channels for the medical community invited Professor Zhang Qingyuan to be interviewed, interpreted research data, and looked forward to the prospects of Darcilla's application.

Sword refers to first -line treatment, Darcille Union

AI general population PFS and ORR innovation high

Darcilla is the first original CDK4/6 inhibitor in China. Based on the significant effect of DAWNA-1 research [2], Darcilla was approved by the National Drug Administration (NMPA) in December 2021. The HR+/HER2-recurring or metastatic breast cancer is used for progress after endocrine therapy.

DAWNA-2 research is another phase III clinical study of Darcilla, which evaluates the efficacy and safety of Darcille combined with AI first-line therapy HR+/HER2-advanced breast cancer. The standard of research in the group is: 1) HR+/HER2-local advanced or metastatic breast cancer proven for pathological confirmation; 2) ECOG PS score 0/1; 3) any menopause state; 4) Treatment; 5) System treatment is not accepted in advanced stages; 6) According to RECIST V1.1, measured diseases or non -measured diseases (dissolved or mixed) of bone lesions (dissolved or mixed). Patients are randomly grouped at 2: 1, and receive 150mg QD+of Darcille (2.5mg QD) or Anenotazo (1mg QD) and placebo+partazozozole treatment. Study on the state of visceral metastasis (yes or no), or whether the previous endocrine (new) auxiliary therapy, and endocrine therapy drugs (来 ornotzole) are layered. The main research finals are PFS (preset unilateral P ≤ 0.0076 for excellent effects) evaluated by researchers.

Figure 1.DAWNA-2 Research Design

The study was included in 456 Chinese patients, of which 303 were Darcille Group and 153 placements of placebo groups. The baseline characteristics of the two groups of patients are basically the same. For example, 60.7%and 60.8%of patients in the Darcilla and the placebo group have internal organs, and 39.6%and 35.3%of patients are pre -menopausal crowds.

As of June 1, 2022, a total of 186 PFS incidents occurred to reach the preset mid -term analysis. The median PFS evaluated by the researchers in the Dalsili group and the placebo group is 30.6 months and 18.2 months, respectively; the risk of death or death by the Dalsley group is 49%(HR = 0.51, 95%CI: 0.38-0.69, P <0.0001). The median PFS evaluated by the Independent Examination Committee (IRC) in the two groups is NR and 22.5 months, respectively; the risk of death or death by the Darcilla's disease is reduced by 50%(HR = 0.50, 95%CI: 0.36-0.70, P <0.0001) Essence

Professor Zhang Qingyuan particularly emphasized, "Among all CDK4/6 inhibitors in patients with HR+/HER2-advanced breast cancer patients, Darcilla PFS exceeded 30 months for the first time, showing the excellent efficacy of Darcilla."

Figure 2. PFS evaluated by researchers

It is worth mentioning that the results of the tumor response indicators evaluated by researchers and IRC also tend to be the Darcilla group. The objective relief rate (ORR) evaluated by the researcher was 57.4%vs 47.7%, respectively; the ORR evaluated by IRC was 62.4%VS 53.6%, respectively. The clinical benefit rate (CBR) evaluated by the researcher was 86.8%VS 79.7%, respectively; the CBR evaluated by IRC was 86.5%VS 75.8%, respectively. Researchers' evaluation of the duration (DOR) is NR and 15 months, respectively; the DOR evaluated by IRC is NR and 20.9 months, respectively. Professor Zhang Qingyuan specifically pointed out, "In the same type of similar types of inhibitors combined with AI first-line treatment, DAWNA-2 studies have reached the current highest ORR."

In terms of security, the adverse reactions of Darcily in DAWNA-2 are similar to the reports reported in previous studies, and no new security signals have appeared. The most common adverse reaction of hematological toxicity is still a decrease in neutral granulocytes, but no fever caused by decreased neutral granulocyte; The median duration of cells is only 3 days. In terms of non -hematological toxicity, Darcilla's liver safety advantages are once again verified, and the incidence of other perceived side effects is low, and the overall safety is good. Focus on patients with metastasis before and after Chinese menopause,

Darcille combined with AI front -line treatment improves PFS

Compared with American patients, Chinese breast cancer patients are younger, and the median diagnosis is about 48-50 years old [3], and about 60%of patients are pre-menopausal state during diagnosis [4]. Professor Zhang Qingyuan pointed out that "young patients have higher requirements for efficacy and quality of life. Patients before menopause may be worse than postmenopausal patients. Therefore, they need to develop good drugs to meet the treatment needs of such patients."

However, reviewing the relevant research of the previous CDK4/6 inhibitors combined with endocrine therapy, except for Monaleesa-7 research, other first-line treatment exploration was only included in postmenopausal patients, so the approved indications did not include pre-menopamental patients. At present, CDK4/6 inhibitors are used to treat HR+/HER2-advanced breast cancer before menopause. In view of the characteristics of the incidence of patients with breast cancer in China, phase III clinical research and discussion of CDK4/6 inhibitors combined with AI in phase III. Important value of patients before menopause.

The mid-term analysis data of the DAWNA-2 research shows [1]. Among the postmenopausal patients, the median PFS of the Darcille Group is 30.6 months, which is significantly extended compared to the placebo group (19.4 months), reducing the progress of disease progress or death risk of death. 48%(HR = 0.52, 95%CI: 0.36-0.75, P = 0.0002); Among the patients before menopause, the two groups of medium-ranked PFS were NR and 16.6 months, respectively. 47%(HR = 0.53, 95%CI: 0.33-0.85, P = 0.0039). The results of other sub -group analysis show that no matter whether the patient's age, whether the previous endocrine therapy, and the expression of hormone receptors can be benefited from the combined treatment of Darcilla.

In addition, the prognosis of patients with visceral metastases is poor and the treatment challenges are great. DAWNA-2 research incorporated nearly 60%of patients with internal organs, and still achieved excellent therapeutic effects. Compared with placebo, Darcilla reduced the risk of disease progress or death of patients by Darcilla (HR = 0.63).

"In general, the Dawna-2 research incorporates about 40%of the pre-menopamental patients, which is more in line with China's clinical reality. It also surpasses the common problem of internal organs in the field of HR+/HER2-breast cancer. The success of this study realizes the full coverage of Darcilla's combination of endocrine therapy before and after menopause HR+/HER2-advanced breast cancer patients, which can benefit to patients with breast cancer in China. "

Or it will become first -line and second -line treatment preferred,

Darcilla's broad application prospects are worth looking forward to

DAWNA-1 and Dawna-2 studies are incorporated into 100%of the Chinese population. Patients before entering the group are more in line with Chinese clinical reality (DAWNA-1 is also included in patients with advanced first-tier accepted chemotherapy), and actively challenged HR+/HER2-advanced breast cancer The difficulty of treating people is not lost to similar CDK4/6 inhibitors, and the security shows its advantages. Judging from the current research progress, whether it is HR+/HER2-late front line or advanced second line, it will become preferred.

Based on the results of DAWNA-1 research, Darcille+Fluvis Group has been incorporated by Grade Ⅰ recommendations after the Failure of AI treatment by the China Clinical Oncology Society (2022 CSCO BC) in 2022. Professor Zhang Qingyuan said, "With the heavy results of DAWNA-2 research, Darcilla combined with the exact evidence of the first-line treatment plan, or it will become a new plan for the first-line treatment of HR+/HER2-advanced breast cancer. Agree, really benefit more patients with breast cancer. "

For patients with HR+/HER2-advanced breast cancer, Darcilla's combination of endocrine therapy significantly improved patients with PFS, extended the time of subsequent chemotherapy, and achieved good results in first-line and second-line treatment, providing reliable evidence-based medical evidence. Darcilla is still layout research to broaden the border of beneficiaries, for example, early new auxiliary (MUKDEN-1 research) in HR+/HER2+breast cancer and the field of advanced first-tier and second-line (Lordships) have gained preliminary efficacy; in HR+/HER2-breast gland Exploration in cancer (new) auxiliary treatment is actively developing. Looking forward to the announcement of more clinical research data confirms the clinical benefits and safety advantages of Darcilla, and bring hope and gospel to more patients with breast cancer.

Expert Introduction

Professor Zhang Qingyuan

Chief physician, second -level professor, doctoral supervisor, provincial teaching teacher

Director of Heilongjiang Provincial Institute of Tumor Prevention and Control

Deputy Dean of Harbin Medical University Affiliated Cancer Hospital

Chief scientist of Harbin Medical University

Harbin Medical University Star Federation Program Outstanding Professor

The leader of the national key college of oncology

Elected by the National Talent Project

The country's outstanding contribution of middle -aged and young experts

Chairman of the lymphatic committee of the Chinese Anti -Cancer Association

Deputy Chairman of the China Anti -Cancer Association Chemotherapy Professional Committee

Deputy Chairman of the Breast Cancer Professional Committee of China Anti -Cancer Association

Deputy Chairman of the China Clinical Oncology Society of Breast Cancer Expert Committee

references:

[1] Binghe xu, qingyuan zhang, pin zhang, et al.dalPiciclib plus Letrozole or Anastrole as 1st-Line Treatment for HR+/Her2-Advanced Breast: A PHASE 3 TRIAL.20202ALAAL.2 TRIAL.

[2]Xu B,Zhang Q,Zhang P,et al.Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer:a randomized,phase 3 trial.Nat Med.2021 Nov;27(11) : 1904-1909.

[3] FAN L, Strasser-Weippl K, Li JJ, ET Al.Breast Cancer in China.lancet oncol.2014 jun; 15 (7): E279-89.

[4] China Early breast cancer ovarian function inhibits clinical application expert consensus (2021 edition) [J]. China Cancer Magazine, 2022,32 (02): 177-190.

*This article is only used to provide scientific information to medical people, and does not represent the viewpoint of this platform

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