Document ID: FDA-2012-D-0432-0001
Agency: fda
Document Type: Notice
Title: Draft Guidance for Industry on Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval
Posted Date: 2012-05-30T04:00Z

[Federal Register Volume 77, Number 104 (Wednesday, May 30, 2012)]
[Notices]
[Pages 31858-31859]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-12928]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0432]

Draft Guidance for Industry on Pathologic Complete Response in 
Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an 
Endpoint To Support Accelerated Approval; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Pathologic 
Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage 
Breast Cancer: Use as an Endpoint to Support Accelerated Approval.'' 
FDA's accelerated approval regulations permit approval of a new drug to 
treat a serious disease on the basis of an effect on a surrogate 
endpoint reasonably likely to predict the clinical benefit of the drug. 
This draft guidance is intended to assist applicants in designing 
trials to support marketing approval of drugs to treat breast cancer in 
the neoadjuvant (preoperative) setting using pathologic complete 
response (pCR) as a surrogate endpoint that could support approval 
under the accelerated approval regulations. Despite advances in 
systemic therapy of early-stage breast cancer over the past few 
decades, there remains a significant unmet medical need for certain 
high-risk or poor prognosis populations of early-stage breast cancer 
patients. This guidance is intended to encourage industry innovation 
and expedite the development of breakthrough therapies to treat high-
risk early-stage breast cancer.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by July 30, 2012.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Tatiana Prowell, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 5249, Silver Spring, MD 20993-0002, 301-
796-2330.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Pathologic Complete Response in Neoadjuvant Treatment of 
High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support 
Accelerated Approval.'' Under the accelerated approval regulations (21 
CFR part 314, subpart H, and 21 CFR part 601, subpart E), FDA may grant 
marketing approval for a new drug on the basis of adequate and well-
controlled trials establishing that the drug has an effect on a 
surrogate endpoint that is reasonably likely to predict clinical 
benefit (e.g., an effect on survival or irreversible morbidity), 
provided that the applicant conducts additional trials after approval 
to verify and describe the predicted clinical benefit. This draft 
guidance is intended to assist applicants in designing trials to 
support marketing approval of drugs to treat breast cancer in the 
neoadjuvant (preoperative) setting using pCR as a surrogate endpoint 
that could support approval under the accelerated approval regulations. 
The guidance proposes a uniform definition of pCR for regulatory 
purposes. The guidance also advises on appropriate patient populations 
for inclusion and on the trial designs intended to verify the predicted 
clinical benefit associated with pCR to support conversion to full 
approval.
    FDA recognizes that despite advances in adjuvant systemic therapy 
of breast cancer over the past few decades, there remains a significant 
unmet medical need for certain high-risk or poor prognosis populations 
of early-stage breast cancer patients. Developing highly effective new 
drugs for these populations is an FDA priority. In providing guidance 
on the use of pCR as a surrogate endpoint that could support 
accelerated approval in the neoadjuvant setting, FDA hopes to encourage 
industry innovation and expedite the development of breakthrough 
therapies to treat high-risk early-stage breast cancer.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the Agency's current thinking on the use of 
pCR in neoadjuvant treatment of high-risk early-stage breast cancer as 
an endpoint to support accelerated approval. It does not create or 
confer any rights for or on any person and does not operate to bind FDA 
or the public. An alternative approach may be used if such approach 
satisfies the requirements of the applicable statutes and regulations.

II. The Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR parts 312 and 314 have 
been approved under OMB control numbers 0910-0014 and 0910-0001, 
respectively. The collections of information for special protocol 
assessments have been approved under OMB control number 0910-0470.

III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. Identify 
comments with the

[[Page 31859]]

docket number found in brackets in the heading of this document. 
Received comments may be seen in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: May 15, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-12928 Filed 5-29-12; 8:45 am]
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