▎ WuXi AppTec content team editor
Recently, a CDK4/6 inhibitor, Dalpiciclib isethionate tablets (trade name: iRrikon), was approved for marketing by the State Drug Administration of China (NMPA) for "combined fulvestrin for patients with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) who have developed disease progression after previous endocrine therapy."
According to the information on the official website of NMPA, the listing of dalcilly tablets of isethionate provides new treatment options for breast cancer patients.
Screenshot source: NMPA official website
One of the most common cancers worldwide
According to the 2020 global cancer burden data released by the World Health Organization's International Agency for Research on Cancer (IARC), breast cancer surpassed lung cancer for the first time to become one of the most common cancers in the world.
In 2020, there were 2.26 million new cases of breast cancer worldwide, accounting for 11.7% of new cancer cases, followed by lung and colorectal cancer. About 1 in 8 new cancer patients are breast cancer patients. In China, there were about 420,000 new cases of breast cancer in 2020 and led to about 120,000 deaths.
According to the molecular classification of breast cancer, breast cancer can be divided into luminal type (HR+), HER2 overexpression type and triple negative breast cancer. Among them, luminal type is the main type of breast cancer, accounting for about 70% of all breast cancers.
Endocrine therapy is the mainstay of treatment for advanced luminal breast cancer, but primary and secondary resistance often lead to treatment failure. For this group of patients, new treatments are urgently needed.
Image credit: 123RF
New treatment options for patients with advanced Luminal breast cancer
CDK4/6, also known as cyclin-dependent kinases 4 and 6, are key regulators that drive cell division and play an important role in the regulation of the cell cycle.
The study found that in most tumors, various genetic or epigenetic changes caused high activity of CDK4/6, which in turn overphosphorylated and inhibited the Rb protein (retinoblastoma protein), ultimately leading to the disorderly proliferation of cancer cells.
Clinical studies have confirmed that more than half of breast cancer patients overexpress cyclin D, and the majority are estrogen receptor-positive (ER+) breast cancer patients. Since cyclin D acts directly on CDK4/6, CDK4/6 has become an important molecular target for patients with luminal-type advanced breast cancer, becoming a new treatment option for this group of patients.
The Guidelines for the Diagnosis and Treatment of Breast Cancer of the Chinese Society of Clinical Oncology (CSCO) (2021 Edition), the Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer in China (2020 Edition) and the Guidelines and Norms for the Diagnosis and Treatment of Breast Cancer of the Chinese Anti-Cancer Association (2021 Edition) recommend the clinical application of CDK4/6 inhibitors combined with endocrine therapy in HR+/HER2-advanced breast cancer.
Significantly reduces the risk of disease progression and death
Darcily is a CDK4/6 inhibitor that selectively inhibits CDK4/6 kinase activity, thereby blocking the CDK4/6-Rb signaling pathway, inducing the blockage of the G1 phase of cells (that is, from mitosis to the period before DNA replication, also known as pre-synthesis, which mainly synthesizes RNA and protein rapidly), and selectively inhibiting the proliferation of Rb protein hyper-expression tumor cells, thereby inhibiting the proliferation of tumor cells.
On November 4, 2021, Nature Medicine, a sub-journal of Nature Medicine, published the results of the interim analysis of the Phase 3 clinical study of HR+/HER2-advanced breast cancer treated by Darcily combined with fulvestrant for the treatment of disease progression following previous endocrine therapy (DAWNA-1 study).
The results of the study show that:
Darcili + fulvesgroup significantly prolonged median progression-free survival (mPFS, 15.7 vs 7.2 months) and reduced the risk of disease progression or death by 58% compared with placebo + fulvestrant.
The most common grade 3 or 4 adverse events in darcili+fulvestrant were neutropenia (84.2%) and leukopenia (62.1%), with similar rates of serious adverse events in both groups (5.8% vs 6.7%).
In addition, several clinical studies of Darcily in HR+ breast cancer are underway, involving therapeutic drugs for breast cancer at different stages of disease development.
We expect this drug to make more clinical research advances and bring new treatment options to more patients."