Appendix 4 to the guideline on the evaluation of anticancer medicinal products in man - condition specific guidance - Scientific guideline

This document is an appendix to the guideline on the evaluation of anticancer medicinal products in man. It provides a guidance on the clinical development for the treatment of specific conditions, including NSCLC, prostate cancer, CML, MDS and HSCT.

Keywords: Non-small cell lung cancer (NSCLC), prostate cancer, chronic myeloid leukemia (CML), myelodysplastic syndormes (MDS), haematopoietic stem cell transplantation (HSCT), breast cancer, pathologic complete response (pCR), neoadjuvant treatment, surrogate endpoint, minimal residual disease (MRD), chronic lymphocytic leukaemia (CLL)

Current effective version - currently under revision, see below

Evaluation of anticancer medicinal products in man - Appendix 4: Condition specific guidance - Revision 2

Adopted Reference Number: EMA/CHMP/703715/2012 Rev.2 Legal effective date: 01/07/2016

Document history - Revision 3

Concept paper on the need to revise appendix 4 (on condition-specific guidance) to the guideline on the evaluation of anticancer medicinal products in man - Revision 3

Draft: consultation closed Consultation dates: 01/04/2017 to 30/06/2017 Reference Number: EMA/102314/2017 Summary:

This concept paper describes and discusses the basis for the revision to the existing Appendix 4 containing disease specific guidance in relation to the use of minimal residual disease as a clinical endpoint in multiple myeloma clinical studies. Appendix 4 is included in the guideline on anticancer medicines. It became a separate appendix as part of the 4th revision of the guideline published in January 2013.

Document history - Revision 2 (current)

Evaluation of anticancer medicinal products in man - Appendix 4: Condition specific guidance - Revision 2

Adopted Reference Number: EMA/CHMP/703715/2012 Rev.2 Legal effective date: 01/07/2016

Document history - Revision 1

Appendix 4 to the guideline on the evaluation of anticancer medicinal products in man - Condition specific guidance - Revision 1

Adopted Reference Number: EMA/CHMP/703715/2012 Rev. 1

Overview of comments received on 'Guideline on the role of the pathological Complete Response (pCR) as an endpoint in neoadjuvant breast cancer studies'

Reference Number: EMA/94983/2015

Concept paper on the need to revise condition–specific guidance, appendix 4 to the guideline on the evaluation of anticancer medicinal products in man - Revision 1

Draft: consultation closed Consultation dates: 31/07/2013 to 31/10/2013 Reference Number: EMA/CHMP/432831/2013 Summary:

The guideline on anticancer medicinal products as revised in early 2010 included disease-specific guidance which was recently expanded to constitute a separate appendix. During the consultation period, stakeholders expressed an interest in further condition-specific guidance, but importantly also in relation to specific issues such as the use of pathological complete remission (pCR) in neoadjuvant studies in breast cancer and minimal residual disease (MRD) in chronic lymphocytic leukaemia and other haematological malignancies as primary endpoints in pivotal studies. This concept paper describes and discusses the basis for this revision to the existing guideline in relation to pCR and MRD.

Draft guideline on the role of the pathological Complete Response as an endpoint in neoadjuvant breast cancer studies

Draft: consultation closed Consultation dates: 28/04/2014 to 31/07/2014 Reference Number: EMA/CHMP/151853/2014 Summary:

Neoadjuvant chemotherapy is commonly used in locally advanced breast cancer (LABC) patients to facilitate breast conserving surgery (Romero et al. Annals of Oncology 24: 655-661, 2013). Currently, disease-free survival (DFS) is considered to be an appropriate endpoint for treatment effect and as a surrogate endpoint for overall survival (OS) (EMA/CHMP/205/95/Rev.4).

Document history - First version

Appendix 4 to the guideline on the evaluation of anticancer medicinal products in man - Condition-specific guidance - First version

Adopted Reference Number: EMA/CHMP/703715/2012 Legal effective date: 01/07/2013

Superseded document - Appendix 2

Appendix 2 to the Guideline on the evaluation of Anticancer Medicinal Products in Man (CPMP/EWP/205/95 Rev. 3) on Confirmatory studies in Haematological Malignancies

Adopted Reference Number: EMA/CHMP/EWP/520088/2008

Overview of comments received on draft appendix 2 to the guideline on the evaluation of anticancer medicinal products in man (CPMP/EWP/205/95 Rev.3) on confirmatory studies in haematological malignancies

Reference Number: EMA/574487/2009

Draft appendix 2 to the guideline on the evaluation of anticancer medicinal products in man (CPMP/EWP/205/95 REV. 3) on haematological malignancies

Draft: consultation closed Reference Number: EMEA/CHMP/EWP/520088/2008

Superseded document

Concept paper on haematological malignancies

Reference Number: EMEA/CHMP/EWP/20808/2008