*For medical professionals only

The DAWNA-2 study adds Chinese evidence-based

The 2022 European Society of Oncology (ESMO) Conference was held

Breast cancer in China shows a trend of rejuvenation, and there are more patients with visceral metastasis and premenopausal diseases

Due to the influence of lifestyle or environmental factors, the age of onset of breast cancer in China is getting younger and younger, with the median age of diagnosis being 48-50 years old^[2], while young breast cancer patients are more likely to develop visceral metastasis, < 40-year-old patients have a 54% incidence of visceral metastasis, and ≥ 40-year-old patients have a (43%)<b11>;[3]; And about 60 percent of patients are in premenopausal status at the time of diagnosis ^[4

"They have more family responsibilities and social responsibilities, so the treatment of such patients should be based on the choice of therapeutic drugs that are safer and more suitable for long-term use while ensuring the efficacy of the patients, so as to ensure the quality of life of

Previous studies of CDK4/6 inhibitors combined with endocrine in the first-line treatment of HR+/HER2-advanced breast cancer were reviewed, with only THE MONALEESA-7 study including premenopausal or perimenopausal patients, and other first-line studies including only postmenopausal patients ^[5-7] with no information

Subgroups with Chinese characteristics were able to benefit from darcily combination therapy, enriching Evidence-Based In China

Professor Pan Yueyin interpreted the subgroup data

According to the latest data released by the ESMO conference, 100% of the 456 patients enrolled in the DAWNA-2 study were Chinese patients, of which 39.

Figure 1.
Benefit of postmenopausal (left) and premenopausal (right) PFS in dawna-2 studies

In the DAWNA-1 study, darcily's group also included 44% of premenopausal patients
.

PFS in premenopausal patients after darcily combined with fulvestrantin was extended by 9.
3 months (18.
7 vs 9.
4 months) and the risk of disease progression or death was reduced by 45%; Postmenopausal patients with a PFS extension of 10.
2 months (15.
7 months vs 5.
5 months) reduces the risk of disease progression or death by 56 percent ^[8].

Figure 2.
Median PFS benefit in premenopausal (top) and postmenopausal (bottom) patients

"The success of the two studies has achieved the comprehensive coverage of Darsili in the first- and second-line therapy combined with endocrine therapy drugs for patients with premenopausal and postmenopausal HR+/HER2-advanced breast cancer, which will benefit Chinese breast cancer patients to a greater extent," professor Pan Yueyin emphasized
.

In addition, 60.
7 percent of patients with visceral metastases were included in the DAWNA-2 study, and the risk of disease progression or death was reduced by 37 percent after treatment with Darsili and AI^[1].
; In the DAWNA-1 study, 58.
9 percent of patients with visceral metastases reduced the risk of disease progression or death by 46 percent after treatment with Darcily plus fulvestrant ^[8].


The DAWNA-1 study also included 27 percent of patients who had received advanced first-line chemotherapy and had a 32 percent lower risk of disease progression or death after combined treatment with Darsili ^[8].


It can be seen that Darsili has achieved treatment benefits in the total population and subgroups in view of the pathogenesis characteristics and diagnosis and treatment status of HR+/HER2-advanced breast cancer in China, bringing more suitable and effective treatment options to
Chinese patients.

Compared with other CDK4/6 inhibitors, Darcily's two Phase III studies were 100% included in the Chinese group, providing Chinese clinicians with Chinese "Da" cases based on clinical trial data from Chinese breast cancer patients
.

And the two studies also included a considerable proportion of premenopausal and visceral metastases (the DAWNA-1 study also included first-line patients who had received chemotherapy), which is closer to the current situation of diagnosis and treatment of Chinese patients and has more reference significance
.

Professor Pan Yueyin also stressed that the success of Darsilly also enlightens us that in the design of clinical trials, we should start from the clinical needs of patients and based on national conditions, explore original research and innovative drugs based on Chinese evidence,, and benefit more Chinese patients
.

Common adverse reactions are easy to manage, liver toxicity is lower, and there are fewer perceived side effects

When talking about Darsili's adverse reaction management experience, Professor Pan Yueyin shared his views, "Darsili's adverse reaction management also has Chinese characteristics, and its related research is 100% included in Chinese patients, and in the management of adverse reactions, more consideration will be given to the disease characteristics of Chinese patients themselves and a reasonable response plan
will be given.
"
”

A review of studies with CDK4/6 inhibitors in combination with endocrine therapy found that neutropenia is a haematological adverse effect common to CDK4/6 inhibitors and may have a higher incidence of neutropenia in Asian ^{populations [5-6].}


The most common adverse effect of the DAWNA-2 study was also neutropenia, but no fever of granulodysciency was observed, and the median duration of neutropenia above level 3 was only 3 days
.

Also, the median time from first to neutropenia is 28 days^[1
].

Symptomatic treatment or dose adjustment can quickly alleviate related adverse reactions, and the current treatment measures are relatively mature and easy to manage
.

In terms of non-hematologic toxicity, the incidence of elevated grade 3 AST and ALT in the Darcily group in the DAWNA-2 study was 1.
7% and 0.
7%, respectively, and no elevation of grade 4 AST and ALT was observed^[1], again supporting Darcily's hepatic safety advantage
.

Darcily introduces piperidine structures through classical electron effusion replacement, eliminating the risk of glutathione capture and avoiding potential hepatotoxicity
.

Considering that Chinese breast cancer patients have a certain percentage of HBV infection ^[9], Darcily may be a more suitable CDK4/6 inhibitor
in patients with underlying liver function impairment.

On the other hand, diarrhea adversely affects the quality of life of patients, with a lower incidence of diarrhea in the Darcily group and no grade 3/4 diarrhea observed ^[1
].

There are few perceived side effects, which is conducive to improving patients' medication compliance and improving patients' quality of life
.

Finally, Professor Pan Yueyin summarized the value and significance
of DAWNA-2 research for breast cancer patients and clinicians in China.

He said that darsily as China's first self-developed CDK4/6 inhibitor, the success of the DAWNA-1 study proved its potency, better liver safety, 100% Chinese evidence-based characteristics
.

In the DAWNA-2 study presented at the ESMO conference, Darcily has continued to perform well, combined with AI first-line treatment of PATIENTs with HR+/HER2-advanced breast cancer with excellent efficacy and controllable safety, easy management, and once again proved its liver safety characteristics
.

This brings more comprehensive and definite survival benefits to Chinese patients, especially premenopausal patients, and also provides more possibilities
for clinicians to explore better treatment strategies in the treatment of HR+/HER2-advanced breast cancer.

We sincerely hope that Darsili will enter medical insurance as soon as possible and benefit more Chinese patients
.

Professor Pan Yueyin

Chief physician of the First Affiliated Hospital of the University of Science and Technology of China, second-level professor, doctoral supervisor Jianghuai famous doctor

Vice President of Anhui Provincial Cancer Hospital

Person in charge of the construction of the national key specialty of oncology

Head of Anhui Provincial Malignant Tumor Immunotherapy Research Center

Executive Director of the Clinical Research Institute of Drugs

Vice Chairman of the CSCO Breast Cancer Expert Committee

Vice Chairman of the CSCO Translational Medicine Committee

Vice Chairman of the CSCO Cardiac Safety Committee

Member of the Standing Committee of the CSCO Lung Cancer Expert Committee

Member of the Standing Committee of the Multidisciplinary Committee on Oncology of the Chinese Medical Doctor Association

He is a national member of the Oncology Branch of the Chinese Medical Doctor Association

Member of the Drug Monitoring Committee of the National Health Commission

Member of the National Cancer Center Breast Cancer Expert Committee

He is a member of the Capacity Building and Continuing Education Committee of the National Health Commission and the deputy head of the Breast Group

Chairman of Anhui Clinical Oncology Society

Chairman-elect of the Oncology Branch of Anhui Medical Association

Vice Chairman of Anhui Anti-Cancer Association

Chairman of the Breast Cancer Committee of Anhui Anti-Cancer Association, etc

He won the first prize of Anhui Provincial Science and Technology Progress Award, and published more than 100 SCI articles
as the first or corresponding author.

References:

[1].
Binghe Xu, Qingyuan Zhang, Pin Zhang, et al.
Dalpiciclib plus letrozole or anastrozole as 1st-line treatment for HR+/HER2- advanced breast cancer (DAWNA-2): a phase 3 trial.
2022 ESMO.
LBA16.

[2].
Fan L, Strasser-Weippl K, Li JJ, et al.
Breast cancer in China.
Lancet Oncol.
2014 Jun; 15(7):e279-89.

[3].
Tjokrowidjaja A, Lee CK, Houssami N, et al.
Metastatic breast cancer in young women: a population-based cohort study to describe risk and prognosis.
Intern Med J.
2014 Aug; 44(8):764-70.

[4].
Expert consensus on the clinical application of ovarian function inhibition in early breast cancer in China (2021 edition)[J].
Chinese Journal of Cancer,2022,32(02):177-190.

[5].
Tripathy D, Im SA, Colleoni M, et al.
Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial.
Lancet Oncol.
2018 Jul; 19(7):904-915.

[6].
Binghe Xu, Xichun Hu, Wei Li, et al.
PALOMA-4: Primary results from a phase III trial of palbociclib (PAL) + letrozole (LET) vs placebo (PBO) + LET in Asian postmenopausal women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative (ER+/HER2–) advanced breast cancer (ABC).
2021 ESMO.
Abstract 228MO.

[7].
Zhang QY, Sun T, Yin YM, et al.
MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study.
Ther Adv Med Oncol.
2020 Oct 22; 12:1758835920963925.

[8].
Pin Zhang, Qingyuan Zhang, Xichun H, et al.
Dalpiciclib plus fulvestrant in HR+/HER2− advanced breast cancer (ABC): updated analysis from the phase 3 DAWNA-1 trial.
2022 ESMO.
Abstract #229P.

[9].
Li N, Zhong QQ, Yang XR, et al.
Prognostic Value of Hepatitis B Virus Infection in Very Young Patients With Curatively Resected Breast Cancer: Analyses From an Endemic Area in China.
Front Oncol.
2020 Aug 7; 10:1403.