The US Food and Drug Administration (FDA) “may require” or seek agreement from sponsors to conduct post-marketing studies to analyze long term effects of breast cancer drugs in both pre- and post-menopausal women in a final guidance issued on 17 June. The guidance also provides other considerations for sponsors as they plan for the inclusion of premenopausal women in clinical trials of drugs for breast cancer treatment.
According to the agency’s announcement of the final guidance, historically, premenopausal women have been excluded from these trials, and in some cases, separate studies have been conducted in this patient population. Yet chemotherapy, immunotherapy and targeted therapies “have similar efficacy in pre- and post-menopausal women with breast cancer.”
The notice said that “based on a review of the literature, FDA believes hormonal drugs administered to premenopausal women with [hormone receptor]-positive breast cancer, with adequate estrogen suppression, are likely to have the same efficacy and safety profile as in postmenopausal women.”
The final guidance updates the previous version by providing more information on the type of long-term follow-up studies that should be conducted by sponsors. The draft said that sponsors should collect information on long-term clinical effects, but did not specify further.
The final version states that “as warranted under applicable law or regulation, FDA may require, or seek agreement from the sponsor to conduct post-marketing studies to analyze additional long-term clinical effects.” The regulations under 21 CFR 312.85 covers Phase 4 postmarketing studies for investigational new drugs under the federal Food, Drug and Cosmetic Act.
This change was sought by Novartis, which in comments submitted after the draft guidance was issued urged the FDA to “provide more guidance on the collection of these long-term effects since these patients will likely participate in future clinical trials” in its comments on the draft.
Novartis also sought more explicit information or guidance regarding levels of follicle-stimulating hormone and estradiol levels that should be used to determine menopausal status, and asked for a definition of premenopausal status. FDA declined to include this level of detail in the final guidance.
The Susan G. Komen Foundation wanted the FDA to collect long-term follow-up data on patients, extending beyond the 5-year mark, along with post-market studies and real-world data collection,to “supplement the data and more fully understand the long-term effects of cancer treatment.” FDA did not incorporate these explicit recommendations.
Another change from the draft guidance urges sponsors to ensure that trials are racially and ethnically diverse. It states that “clinical studies evaluating drugs in pre-menopausal women with breast cancer should reflect the racial and ethnic diversity of this patient population to support the assessment of short- and long-term effects of these therapies across clinically relevant subgroups of patients.”
The guidance also encourages sponsors to meet with the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research, as appropriate, to discuss their breast cancer drug development plans early in development.
The guidance finalizes a draft guidance issued last October 2020. (RELATED: FDA: Include premenopausal women in breast cancer trials, Regulatory Focus 7 October 2020)
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.