The CDK4/6 inhibitor is another important breakthrough in breast cancer treatment, and as the “big brother,” piperacillin (Palbociclib) has been approved for marketing by the US Food and Drug Administration (FDA). It is currently available for first-line and second-line treatment:
First-line therapy refers to the combination of piperacillin with an aromatase inhibitor for the initial treatment of hormone receptor-positive, HER2-negative, advanced postmenopausal breast cancer. Second-line therapy refers to the combination of endocrine agents or fulvestrant in advanced breast cancer that has become resistant to endocrine agents.
Piperacillin is currently available in China and has not yet been given an indication for second-line therapy. However, endocrine-resistant patients still have the opportunity to participate in relevant clinical trials or to use the drug under the guidance of their physicians.
World’s first CDK4/6 inhibitor
Piperacillin is the world’s first CDK4/6 inhibitor. CDK4/6, the full Chinese name for cell cycle protein-dependent kinase (CDK) 4 and 6, is an essential catalyst in the continuous cycle of cell division and proliferation.
By preventing CDK from functioning, the cell cycle is interrupted and cells cannot continue to proliferate. This is how CDK inhibitors work to kill cancer cells.
However, selective inhibition of CDK can also affect normal cells. Piperacillin is a selective CDK inhibitor, and as the name implies, it only acts selectively on CDK 4 and 6. Hormone receptor-positive breast cancer cells are such CDK 4/6-activated cells, so piperacillin can be more targeted in its anti-cancer effects.
Piperacillin plus fulvestrant slows tumor progression in second-line therapy
The PALOMA-3 phase III clinical trial provides evidence for piperacillin in second-line therapy. The study was conducted in patients with hormone receptor-positive, HER2-negative advanced breast cancer whose tumors had recurred or progressed after failure of prior endocrine therapy.
In 521 patients, the median progression-free survival time for piperacillin + fulvestrant treatment was 9.2 months compared with 3.8 months for fulvestrant alone. Piperacillin delayed tumor progression by a remarkable 5.4 months.
While the addition of piperacillin may have increased the side effects of the drug, overall it was well tolerated by patients.
Watch and wait to explore in more breast cancers
Many tumor cells are overactive for CDK4/6, so the indications for piperacillin in breast cancer are expected to continue to expand. The following explorations are of interest:
- Moving toward early-stage breast cancer. Investigators are gradually moving from advanced breast cancer to early breast cancer. One study used piperacillin as adjuvant therapy in postmenopausal patients with hormone receptor-positive, HER2-negative early-stage breast cancer.
- A combination of different drugs. In addition to letrozole and fulvestrant, investigators have looked at the effects of combining piperacillin with another endocrine drug, tamoxifen.
- Comparison with other therapies. Investigators will compare piperacillin with other therapies (such as chemotherapy) to find more appropriate dosing regimens and combinations. For example, they will compare the difference in efficacy between piperacillin + endocrine therapy and capecitabine chemotherapy.
Piperacillin in China
Piperacillin is now available in China. The Chinese Society of Clinical Oncology breast cancer guidelines encourage patients to participate in clinical studies and include CDK4/6 inhibitors as an optional endocrine combination for advanced breast cancer.
Summary
Piperacillin is used in HR-positive, HER2-negative advanced or metastatic breast cancer, and in patients with progressive disease after endocrine therapy, fulvestrant in combination with piperacillin in second-line therapy may extend progression-free survival by 5.4 months.
More exploration of piperacillin is ongoing, and it is expected that these studies will produce solid evidence.