About 60% of patients who get breast cancer after menopause can be found to be estrogen or progesterone receptor positive, and these patients have estrogen- and progesterone-related disease [1] that can be treated with hormone suppression. This is what we know as endocrine therapy.
In recent years, a new class of targeted drugs, CDK4/6 inhibitors, have emerged, and they can be very effective in combination with endocrine therapy. The following three CDK4/6 inhibitors are currently available in the United States, of which piperacillin is already available in China:
- Piperacillin (trade name: Epoxin)
- Ribociclib (trade name: Kisqali)
- Abemaciclib (trade name: Verzenio)
All three of these new drugs are used in patients with hormone receptor-positive, HER2-negative, postmenopausal advanced breast cancer, but there are differences in combination regimens, timing of dosing, and efficacy, which are described in more detail below.
Which drug works best? How do I choose?
CDK4/6 inhibitors combined with endocrinologic agents are the best combination for first-line therapy
First, all three of these drugs combined with an aromatase inhibitor can be used as “first-line therapy,” or preferred therapy, in patients who meet the above criteria. What is an “aromatase inhibitor”? This is a class of “traditional” endocrine therapies, including letrozole (Fury), anastrozole (Renintex), and exemestane (Anoxin), which block estrogen production and are usually used in postmenopausal women.
Despite the same setting and regimen, there was a slight difference in efficacy from the study data, with a median progression-free survival of 27.6 months for patients with piperacillin (14.5 months with endocrine therapy alone) compared with 25.3 months and 28.2 months for the combination regimen of Ribociclib and Abemaciclib, respectively (16 months and 14.8 months).
The study design was similar for all 3 drugs, although there was no two-by-two comparison. When comparing the efficacy of the 3 drugs, it was found that Abemaciclib prolonged the longest median progression-free survival at first-line treatment. The median progression-free survival is the value of the time spent in the middle of the line for all patients whose tumors remained stable after treatment.
Second-line therapy: both piperacillin and Abemaciclib as options
In addition to being first-line therapy, piperacillin and Abemaciclib can be used in combination with fulvestrant for second-line therapy in patients who meet the above criteria, that is, as an option after failure of first-line therapy.
Fulvestrant is another commonly used class of endocrine therapy that inhibits the receptors for estrogen and indirectly blocks the effects of estrogen.
From the study data, the median progression-free survival was 9.5 months with piperacillin (4.6 months with endocrine therapy alone) compared with 16.4 months with Abemaciclib (9.3 months with endocrine therapy alone). Comparing the efficacy data, Abemaciclib was slightly better than piperacillin.
Table 2 Combination regimens, timing of dosing, and efficacy of the three CDK4/6 inhibitors
| Drugs | Co-medications | Timing of medication |
Efficacy (median progression-free survival time) |
|
| Co-regimen |
Standard treatment |
|||
| Piperacillin | Aromatase inhibitors | First-line |
Over 27.6 months |
14.5 months |
| Fulvestrant |
Second line |
over 9.5 months | 4.6 months | |
| Ribociclib | Aromatase inhibitors | First-line |
Over 25.3 months |
16.0 months |
| Aromatase inhibitors | First-line | over 28.2 months | 14.8 months | |
| Fulvestrant | Second-line | over 16.4 months | 9.3 months | |
What are the adverse effects?
The three CDK4/6 inhibitors mentioned above have similar adverse effects, commonly including bone marrow suppression (anemia, leukopenia, thrombocytopenia, etc.), gastrointestinal symptoms (nausea, vomiting, diarrhea, decreased appetite), and fatigue, hair loss, diarrhea, etc. Serious adverse effects are rare.