Piperacil (Palbociclib) is one of the hottest CDK4/6 inhibitors in breast cancer in recent years. in February 2015, it received marketing approval from the US Food and Drug Administration (FDA) for advanced breast cancer treatment.
One of the current indications for piperacillin is in combination with letrozole for the first-line treatment of postmenopausal hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer. Piperacillin is already available in China for this indication.
World’s first approved CDK4/6 inhibitor
Piperacil is the world’s first CDK4/6 inhibitor approved for breast cancer, CDK4/6, the full Chinese name for cell cycle protein-dependent kinases (CDK) 4 and 6. In the continuous cycle of the cell cycle, cells undergo constant division and proliferation, and CDK is an essential catalyst in this process, contributing to the completion of the cell cycle. Therefore, by preventing CDK from functioning, the cell cycle is interrupted and cells cannot continue to proliferate.
However, indiscriminate inhibition of CDK necessarily affects normal cells as well. Piperacillin is a selective CDK inhibitor that, as the name implies, only selectively inhibits CDK 4/6. This means that the ability of piperacillin to block the cell cycle is primarily exerted in cells with active CDK4/6.
Estrogen receptor-positive breast cancer cells are such CDK 4/6-active cells, and piperacillin can selectively fight ER-positive breast cancer cells with minimal disruption to normal cells.
First-line combination with letrozole dramatically improves time to control advanced disease
Piperacillin received accelerated marketing approval from the FDA thanks to this key study.
This phase II clinical study, code-named PALOMA-1, enrolled 165 postmenopausal hormone receptor-positive, but HER2-negative patients with advanced breast cancer who had not been previously treated with other breast cancer drugs.
The results showed that the median progression-free survival for breast cancer was almost double in patients treated with piperacillin in combination with letrozole compared with letrozole alone (10.2 months and 20.2 months, respectively).
In terms of adverse effects, common ones included neutropenia, leukopenia, anemia, and fatigue, with no particular side effects seen with the addition of piperacillin.
In the absence of serious adverse reactions, piperacillin delayed the progression of breast cancer by 10 months, making it a successful drug for marketing approval based on the results of a phase II clinical trial alone.
More to explore
Many tumor cells are overactive for CDK4/6, so the indications for piperacillin in breast cancer are expected to continue to grow. According to information from relevant clinical trials, although phase III clinical studies of piperacillin in breast cancer have focused on hormone receptor-positive, HER2-negative breast cancer, the drug has been explored in other areas:
- For breast cancers of different stages: Investigators are shifting their focus from advanced breast cancer to early breast cancer.
- In combination with different drugs: In addition to letrozole and fulvestrant, investigators have looked at the efficacy of piperacillin in combination with tamoxifen.
- Comparison with different regimens: In addition to piperacillin-containing regimens being compared with endocrine therapy, comparative studies of other therapies are also underway.
- Focus on Asian populations: Asia, particularly China, has a large number of breast cancer patients, and investigators are also focusing on the benefits of treatment in this population.
What is the status of piperacillin research in China?
Piperacillin is available in China, and the Chinese Society of Clinical Oncology (CSCO) guidelines encourage patients to participate in relevant clinical studies. One of these is a phase I clinical trial looking at piperacillin in postmenopausal estrogen receptor-positive, HER2-negative advanced breast cancer. The study has now completed patient recruitment.
Summary
Piperacillin is used in HR-positive, HER2-negative advanced or metastatic breast cancer, and in first-line therapy, combining it with letrozole may extend progression-free survival by 10 months.
Studies of piperacillin in more staged breast cancers, in combination with more drugs, and in Asian patients are ongoing, and more data are expected.