On October 7, 2020, the FDA issued a draft guidance encouraging the inclusion of premenopausal women in breast cancer clinical trials.
Premenopausal women are often excluded from trials that investigate the efficacy of drugs in hormone receptor (HR)-positive breast cancer, which is the basis of the guidance. Certain groups of drugs have similar efficacy in pre- and post-menopausal women with breast cancer. Thus, studies are often conducted separately with premenopausal women to demonstrate the benefit of therapies in this population, resulting in delays in the availability of therapies.
Based upon a review of the nonclinical, clinical pharmacology, and clinical literature, the FDA believes that drugs targeting the hormonal axis administered to estrogen-suppressed premenopausal women will have similar efficacy and safety profiles as in postmenopausal women.
The FDA encourages sponsors to discuss their breast cancer drug development plan with CDER and CBER in early development.
The guidance recommendations include:
- Menopausal status should not be the basis of exclusion from any breast cancer clinical trial.
- Premenopausal women with adequate estrogen suppression and postmenopausal women should be equally eligible and included in clinical trials for drugs or combinations manipulating the hormonal axis.
- Stratification of randomization based on menopausal status at study entry may be appropriate if there are efficacy and/or safety concerns.
- An assessment of the weight of evidence that includes published literature and existing nonclinical data for reproductive toxicity should be provided to allow FDA to determine if reproductive toxicity studies may be necessary for an indication that will include premenopausal women.
- Information on long-term clinical effects (e.g., bone health, cardiac health) of breast cancer drugs in premenopausal women should be collected during the trial.
- A gynecologist should be consulted during trial planning and monitoring, as needed.
“Once finalized, we hope that the recommendations in the draft guidance will encourage expanded drug development for the treatment of breast cancer in premenopausal women," explained Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. —Lisa Kuhns
Source: US Food and Drug Administration. FDA In Brief: FDA Encourages Inclusion of Premenopausal Women in Breast Cancer Clinical Trials. October 7, 2020. https://www.fda.gov/news-events/fda-newsroom/fda-brief-fda-encourages-inclusion-premenopausal-women-breast-cancer-clinical-trials
