Breast Cancer Trials Studying CDK4/6 That Have Included Men
Selected breast cancer clinical trials studying CDK4/6 inhibitors have included men, though the data is limited primarily to the COMPLEEMENT-1 trial which specifically evaluated ribociclib in male patients with hormone receptor-positive, HER2-negative advanced breast cancer. 1
Key Trials Including Men
Trials with Confirmed Male Participation:
- COMPLEEMENT-1 (NCT02941926)
- This open-label, multicenter clinical study evaluated ribociclib in combination with letrozole and goserelin/leuprolide for HR-positive, HER2-negative advanced breast cancer
- Included 39 male patients who received KISQALI 600 mg orally once daily (21 days on, 7 days off)
- Male patients also received letrozole 2.5 mg daily and goserelin 3.6 mg or leuprolide 7.5 mg
- Results showed a 46.9% overall response rate in male patients with measurable disease 1
Other CDK4/6 Inhibitor Trials:
The ASCO guidelines for management of male breast cancer note that "selected trials of these targeted agents have included men and small case series have been reported" 2. However, specific trial names beyond COMPLEEMENT-1 are not explicitly mentioned in the evidence.
Clinical Implications for Male Breast Cancer Patients
The ASCO guidelines make several important recommendations regarding CDK4/6 inhibitors in men:
- CDK4/6 inhibitors can be used in men with metastatic hormone receptor-positive, HER2-negative breast cancer as they are used in women 2
- For men with advanced or metastatic HR-positive, HER2-negative breast cancer, endocrine therapy combined with CDK4/6 inhibitors is recommended as first-line therapy (except in cases of visceral crisis or rapidly progressive disease) 2
- The FDA has granted approval for the use of CDK4/6 inhibitors in men with metastatic hormone receptor-positive breast cancer 2
Treatment Considerations for Men
When using CDK4/6 inhibitors in men:
- Men should receive a GnRH agonist (such as goserelin or leuprolide) when treated with aromatase inhibitors plus CDK4/6 inhibitors 2, 1
- Treatment options include tamoxifen, an aromatase inhibitor with a GnRH agent, and fulvestrant, all of which can be combined with CDK4/6 inhibitors 2
- The ESMO guidelines confirm that CDK4/6 inhibitors are effective in men (with an LH-RH agonist) 2
Gaps and Limitations
- Data on CDK4/6 inhibitors in male breast cancer patients remains sparse compared to female patients 2
- Most recommendations for treating male breast cancer with CDK4/6 inhibitors are extrapolated from studies conducted in women 2
- The FDA has encouraged inclusion of men in breast cancer clinical trials, which should improve data availability in the future 2
Future Directions
The inclusion of men in breast cancer clinical trials is increasing, with the FDA recently issuing guidance encouraging the inclusion of male patients in clinical trials studying treatments for breast cancer 2. This should lead to more robust data on the efficacy and safety of CDK4/6 inhibitors in men with breast cancer.