Male Breast Cancer: Developing Drugs for Treatment: Guidance for Industry

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Male Breast Cancer:
Developing Drugs for
Treatment
Guidance for Industry
U.S. Department of Health and Human Services
Food and Drug Administration
Oncology Center of Excellence (OCE)
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
August 2020
Clinical/Medical

Male Breast Cancer:
Developing Drugs for
Treatment
Guidance for Industry
Additional copies are available from:
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Center for Drug Evaluation and Research
Food and Drug Administration
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor
Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: druginfo@fda.hhs.gov
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs
and/or
Office of Communication, Outreach, and Development
Center for Biologics Evaluation and Research
Food and Drug Administration
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Silver Spring, MD 20993-0002
Phone: 800-835-4709 or 240-402-8010; Email: ocod@fda.hhs.gov
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-
guidances
U.S. Department of Health and Human Services
Food and Drug Administration
Oncology Center of Excellence (OCE)
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
August 2020
Clinical/Medical

Contains Nonbinding Recommendations
TABLE OF CONTENTS
I. 	INTRODUCTION............................................................................................................. 1
II. 	BACKGROUND ............................................................................................................... 1
III. 	RECOMMENDATIONS.................................................................................................. 2

Contains Nonbinding Recommendations
1
Male Breast Cancer: Developing Drugs for Treatment
Guidance for Industry1
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the
title page.
I. 	INTRODUCTION
This guidance provides recommendations to sponsors regarding the development and labeling of
cancer drugs, including biological products,2 regulated by CDER and CBER for the treatment of
male patients with breast cancer.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
as recommendations, unless specific regulatory or statutory requirements are cited. The use of
the word should in Agency guidances means that something is suggested or recommended, but
not required.
II. 	BACKGROUND
Breast cancer is rare in males, with less than one percent of all breast cancer cases occurring in
male patients. In addition, males are more likely to be diagnosed at an older age, with a more
advanced stage of disease, and are more likely to have lymph node involvement compared to
females with breast cancer.
Males have historically been excluded from clinical trials of breast cancer drugs because breast
cancer in males is rare. This exclusion has resulted in limited FDA-approved treatment options
for males with breast cancer. Treatment strategies for males with breast cancer are not based on
data from prospective, randomized clinical trials. Rather, clinical management of male breast
cancer is generally based on clinical experience with breast cancer in females and data from
studies conducted in females with breast cancer.
1 This guidance has been prepared by the Oncology Center of Excellence, the Center for Drug Evaluation and
Research (CDER), and the Center for Biologics Evaluation and Research (CBER) at the Food and Drug
Administration.
2 For the purposes of this guidance, references to drugs include drugs approved under section 505 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 355) and biological products licensed under section 351 of the Public
Health Service Act (42 U.S.C. 262).

Contains Nonbinding Recommendations
2
III. 	RECOMMENDATIONS
FDA encourages sponsors to discuss their breast cancer drug development plan early in
development with CDER or CBER, as applicable. These discussions may include expectations
related to the number of male patients and data in male patients for specific development
programs. FDA recommends the following:
• 	Eligibility criteria for clinical trials of breast cancer drugs should allow for inclusion of
both males and females
o 	Scientific rationale should be included in the protocol when proposing to exclude
males from breast cancer trials. FDA does not intend to consider low expected
accrual rates of male patients with breast cancer to be a sufficient scientific
rationale for excluding them from a clinical trial.
• 	When males have not been included or when inclusion of males is very limited in clinical
trials for a specific breast cancer drug:
o 	It may be possible to extrapolate findings to include male patients in the FDA-
approved indication for the drug where no difference in efficacy or safety is
anticipated between males and females based on the mechanism of action of a
drug. The use of extrapolation should be supported by, for example, data from
earlier stages of development (e.g., nonclinical testing), literature, or both.
o 	Further clinical data may be necessary to support extrapolation of findings to
support an FDA-approved indication for male patients with breast cancer where
there is a concern for differential efficacy or safety between males and females.
In breast cancer, this may be relevant when a drug results in or relies upon
manipulation of the hormonal axis, as with endocrine therapy. The additional
data to support efficacy and safety for male patients with breast cancer can be
generated through a variety of trial designs using different data sources, including
small single-arm trials and studies using real-world data sources.
• 	In general, when males are included in clinical trials evaluating breast cancer drugs,
sponsors should conduct nonclinical general toxicology studies in male and female
animals.3, 4
3 For nonclinical data needed to support clinical trial design and marketing applications, refer to ICH guidance for
industry S9 Nonclinical Evaluation for Anticancer Pharmaceuticals (March 2010), ICH guidance for industry S9
Nonclinical Evaluation for Anticancer Pharmaceuticals Questions and Answers (June 2018), and guidance for
industry Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations (May 2019).
We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
4 The Agency supports the principles of the 3Rs to reduce, refine, and replace animal use in testing when feasible.
Sponsors can consult with the Agency if they wish to use other testing methods or strategies. The Agency will
consider whether such an alternative method or strategy could be used instead of an animal study.