Hengrui’s asset Dalpiciclib, the 4th CDK4/6 inhibitor effective in first-line HR+/HER2-advanced breast cancer

Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is the most common and accounts for approximately 70% of all new cases, or nearly 400,000 diagnoses worldwide each year. Almost one in three cases of early-stage breast cancer eventually become metastatic, and among patients with HR+/HER2- metastatic disease, the five-year relative survival rate is 30%. According to the GLOBOCAN 2020 report, breast cancer has become the number one malignant tumor in the world and one of the most common malignant tumors in women. In 2020, there were about 416,000 new cases of breast cancer in China and about 117,000 deaths. At present, the incidence of breast cancer has increased rapidly, and it has ranked first in the incidence of female tumors. Nearly 50% of patients will experience recurrence and metastasis after treatment. Hormone receptor (HR)-positive breast cancer accounts for about 70% of all breast cancers.

Recently, in January 2022, The National Medical Products Administration (NMPA) approved the New Drug Application (NDA) for dalpiciclib in combination with fulvestrant for the treatment of relapsed/progressed HR+/HER2- advanced breast cancer. The company is now evaluating different trials, including 1st line (NCT03966898) and ≥2nd line (NCT03927456) for the treatment of HR+/HER2- advanced breast cancer and adjuvant therapy (NCT04842617) of HR+/HER2- early-stage breast cancer. 

With the data cutoff date of June 01, 2022, around 70.5 % of the total expected observed PFS events occurred at a median follow-up of 21 months. Moreover, the median PFS of dalpiciclib in the top executive group was 30.6 months, while in the placebo group, the median PFS was 18.2 months. Interestingly, the PFS benefit with dalpiciclib + letrozole/anastrozole was consistent in postmenopausal women and pre-or perimenopausal women. As per the investigator, the ORR was found to be 57.4%, followed by the CBR, which was 86.8%. In terms of safety, the drug demonstrated a manageable safety profile, with the most frequent grade ≥3 AEs in the dalpiciclib group was neutropenia and leukopenia. The SAEs occurred in 11.9% in the dalpiciclib group and 6.5% in the placebo group.

Conclusion- These new effective interim results may surely give an advantage to dalpiciclib in the first-line treatment setting and fulfill the unmet need of the patients with HR+/HER2-advanced breast cancer. As we already know that the current first-line market is being led by CDK4/6 inhibitors, mainly Pfizer’s Palbociclib, which is the leading molecule in this setting. It has also got the first-mover advantage in the first and second-line setting and generated approximately USD 5.4 billion worldwide in 2021. With a high dominance level of CDK4/6 Inhibitors, dalpiciclib became the first domestically developed CDK4/6 inhibitor that gained marketing approval in China. Among the approved therapies, CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) have attracted the most attention. Furthermore, Dalpiciclib is the 4th CDK4/6 inhibitor showing survival benefits with letrozole or anastrozole in untreated HR+/HER2- ABC (advanced breast cancer) or with fulvestrant in pretreated HR+/HER2- ABC, in addition to palbociclib, ribociclib, and abemaciclib.

Expert Opinion: “These findings support dalpiciclib + letrozole/anastrozole as a new first-line treatment option in patients with untreated HR+/HER2- advanced Breast Cancer “

“It appears that we will have to choose among four CDK4/6 inhibitors in the coming future.”

For more insights into the breast domain, visit: ER positive HER2 negative Breast Cancer, HER2 positive Breast Cancer, Triple Negative Breast Cancer (TNBC)