Comprehensive description of palbociclib

Palisib (brand name: IBRANCE) is the world's first commercially available CDK4/6 kinase inhibitor, approved by the US FDA through the accelerated approval pathway on February 3, 2015. Developed by Pfizer, this drug is indicated for use in combination with letrozole in the treatment of postmenopausal women with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as an initial endocrine therapy regimen. Its approval is based on clinical data demonstrating a significant prolongation of progression-free survival (PFS), marking an important advancement in the treatment of hormone receptor-positive advanced breast cancer.

Dosage form and usage

• Dosage form and specification: Capsules, 21 capsules per bottle, with specifications including 75mg, 100mg, and 125mg.

• Recommended dosage: Take 125mg once daily with meals, continue for 21 consecutive days, then discontinue for 7 days (with a 28-day cycle). The dosage should be adjusted based on patient tolerance.

• Joint program:

1. First-line treatment: Combined with letrozole (2.5mg/day);

2. After endocrine progression: use in combination with fulvestrant (500mg, injected according to the standard regimen).

Key clinical trial data

1. PALOMA-2 study (first-line treatment):

• Palbociclib combined with letrozole vs. letrozole alone, with median PFS of 24.8 months vs. 14.5 months, respectively, significantly reducing the risk of disease progression.

2. PALOMA-3 study (progression after endocrine therapy):

• Palbociclib combined with fulvestrant vs. fulvestrant monotherapy, the median PFS was significantly prolonged (approximately 5 months), and benefits were observed regardless of ESR1 mutation status.

Mechanism of action and characteristics

Palisperinib is an oral targeted inhibitor that restores cell cycle control and blocks tumor cell proliferation by selectively inhibiting cyclin-dependent kinase 4/6 (CDK4/6). Its advantages include:

• Innovative mechanism: The first targeted drug targeting CDK4/6;

• Remarkable efficacy: Compared to traditional endocrine monotherapy, the combination regimen significantly prolongs PFS;

• Good safety profile: The main adverse reaction is bone marrow suppression (such as neutropenia), but it is mostly manageable. Oral administration is convenient, and patient compliance is high.

"Precautions"

• Common adverse reactions include neutropenia, fatigue, anemia, upper respiratory tract infection, etc. During treatment, regular monitoring of blood routine examination is required;

• Avoid combination with strong CYP3A inhibitors or inducers;

• It has embryofetal toxicity, so women of childbearing age need to take effective contraception.

Conclusion

As a representative of CDK4/6 inhibitors, palbociclib provides an important treatment option for patients with HR+/HER2- advanced breast cancer. Whether used in combination with letrozole for first-line treatment or in combination with fulvestrant after endocrine resistance, it has shown significant clinical benefits in prolonging progression-free survival, marking a positive shift in the treatment paradigm for these patients. With the conduct of more research in the future, its application prospects are expected to be further expanded.