Medical experts discuss treatment strategies and sequencing after ET + CDK4/6i for ER+/HER2- metastatic breast cancer

 

Medical experts discuss treatment strategies and sequencing after ET + CDK4/6i for ER+/HER2- metastatic breast cancer

 

In this conference update video, Profs. Shaheenah Dawood, Heather McArthur, Javier Cortés, and Frédérique Penault-Llorca provide key insights from the highly anticipated 13thAsia-Pacific Breast Cancer Summit (APBCS) Satellite Symposium, sponsored by Menarini Stemline.

 

The esteemed faculty discusses treatment strategies and sequencing options after ET + CDK4/6i for patients with ER+/HER2- metastatic breast cancer (mBC). 

 

Topics of discussion include: 

  • Overview of the ESMO mBC living guidelines 
  • Overcoming endocrine resistance after 1st line ET+CDK4/6i (intrinsic & acquired)  
  • The benefit of biomarker-selected endocrine-based therapies in ER+/HER2- mBC
  • ESR1 mutation: clinical significance and testing strategies 

 

Clinical takeaways

  • ET + CDK4/6i remains the SOC for 1st line treatment in ER+/HER2- mBC. Guidelines recommend exhausting sequential ET-based regimens in the 2nd line setting (as monotherapy or combinations).
  • The challenge of treating ER+/HER2− BC after 1st line ET+CDK4/6i is to overcome endocrine resistance. Molecular resistance patterns include intrinsic alterations and acquired resistance mechanisms (e.g. ESR1-mut). 
  • Elacestrant provides clinically meaningful improvements in PFS for patients with ER+/HER2- mBC who received at least 12 months of ET+CDK4/6i in 1st line and whose tumours harbour ESR1-mut. This benefit was consistent across clinically relevant subgroups. 
  • Safety analyses demonstrated that elacestrant had a manageable safety profile similar to other ETs and without evidence of some of the toxicities associated with other drug classes, such as CDK4/6i and PI3K/AKT/mTOR inhibitors.
  • ESR1-mut testing should be done at 1st line progression via liquid biopsy due to disease subclonality; if negative, repeat at each progression. Archival tissue should not be used for testing due to the acquired nature of ESR1-mut. 

Shaheenah Dawood is a Consultant medical oncologist and professor in clinical oncology in the United Arab Emirates. She trained in medical oncology at McGill University Hospitals in Canada and subspecialized in breast cancer management at MD Anderson Cancer Center. During her training she was awarded multiple scholar in training awards and ASCO merit awards. She has served as an editorial fellow at the New England Journal of medicine and has an MPH from the Harvard School of Public Health. She has over 100 papers to her credit including 50 peer review original articles, 30 review articles and 12 book chapters. She serves as a reviewer for multiple journals. She currently leads the oncology clinical trials program at Mediclinic City Hospital Dubai. She also serves as president of the Excellence in oncology summit that is held annually in Dubai and is co president of the Asia pacific breast cancer summit (ABCS) and Asia pacific gastrointestinal cancer summit (APGCS). She has also recently launched the international BRCA forum and young womens forum.

Prof. Shaheenah Dawood has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

MSD, Roche, BMS, New Bridge, Novartis, llilly , Pfizer, Caris, Merck, Jaansen, Ipsen,Astrazeneca, Zulleg Pharma

Professor of internal medicine at UT Southwestern Medical Center and a member of the Division of Hematology and Oncology. Clinical Director of the Breast Cancer Program at Simmons Cancer Center and specializes in breast cancer research and treatment.

Prof. Heather McArthur has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Amgen, AstraZeneca, BeiGene, Boston Scientific, Bristol-Myers Squibb, Calithera, Celgene, Daiichi-Sankyo, Delcath Systems Inc., Eli Lilly, Genentech/Roche, Gilead, Immunomedics, Merck, Moderna, Novartis, OBI Pharma, Peregrine, Pfizer/Seattle Genetics, Puma, Spectrum Pharmaceuticals, Stemline Therapeutics, Syndax Pharmaceuticals,TapImmune, Bristol-Myers Squibb, MedImmune, LLC/AstraZeneca; BTG; and Merck.

Head of the International Breast Cancer Centre (IBCC) in Barcelona, founding partner of Medica Scientia innovation Research (MedSIR), a company involved in the clinical development of clinical trials. Member of the Scientific Committee of the ESMO and EBCC.

Prof. Javier Cortés has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Roche , AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharp & Dohme, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Scorpion Therapeutics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, Abbvie, BridgeBio, Biontech, Biocon, Circle Pharma, Delcath Systems, Roche, Novartis, Eisai, Pfizer, Lilly, Merck Sharp & Dohme, Daiichi Sankyo, Astrazeneca, Gilead, Stemline Therapeutics.

Frédérique PENAULT-LLORCA, MD, PhD, graduated as a medical specialist in pathology in 1993 and in oncology in 1995. Also, in 1995, she received a PhD from the Université d’Aix-Marseille II in cellular biology and microbiology, on the topic of HER2. Frédérique PENAULT-LLORCA is currently professor of pathology at the University of Clermont-Ferrand, CEO of the Comprehensive Regional Cancer Institute Centre Jean PERRIN, Clermont-Ferrand, France, deputy director of the research team INSERM 1240 IMoST, and head of the Molecular Biology Plateform at Centre Jean Perrin. She serves as vice-president of the UNICANCER group and chairs of the Immuno-Oncology group at UNICANCER R&D. She is a member of several pathology and oncology societies, with her main areas of expertise being female cancers. She co-chairs the French breast cancer guidelines of Nice-St Paul. Frédérique PENAULT-LLORCA has conducted various biomarkers-based research studies in breast, lung, digestive tract, prostate and thyroid cancer in relation to response to targeted therapies and immunotherapies. Frédérique PENAULT-LLORCA has participated to more than 469 peer-reviewed publications and several books on female cancers and pathologic testing methods and issues.

Prof. Frédérique Penault-Llorca has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

AbbVie, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Genomic Health, Gilead, GSK, Lilly, Menarini /Stemline, MERCK, MSD, Myriad, NanoString Technologies, Novartis, Pfizer, Pierre-Fabre, Roche, Seagen, Servier, Tesaro; Institutional research grants from  AbbVie, Agendia, AstraZeneca, Bayer, BMS, Genomic Health, MSD, Myriad, NanoString Technologies, Roche; Congress invitations from AbbVie, AstraZeneca, BMS, MSD, Novartis, Pfizer, Roche 

In this conference update video, Profs. Shaheenah Dawood, Heather McArthur, Javier Cortés, and Frédérique Penault-Llorca provide key insights from the highly anticipated 13thAsia-Pacific Breast Cancer Summit (APBCS) Satellite Symposium, sponsored by Menarini Stemline.

 

The esteemed faculty discusses treatment strategies and sequencing options after ET + CDK4/6i for patients with ER+/HER2- metastatic breast cancer (mBC). 

 

Topics of discussion include: 

  • Overview of the ESMO mBC living guidelines 
  • Overcoming endocrine resistance after 1st line ET+CDK4/6i (intrinsic & acquired)  
  • The benefit of biomarker-selected endocrine-based therapies in ER+/HER2- mBC
  • ESR1 mutation: clinical significance and testing strategies 

 

Clinical takeaways

  • ET + CDK4/6i remains the SOC for 1st line treatment in ER+/HER2- mBC. Guidelines recommend exhausting sequential ET-based regimens in the 2nd line setting (as monotherapy or combinations).
  • The challenge of treating ER+/HER2− BC after 1st line ET+CDK4/6i is to overcome endocrine resistance. Molecular resistance patterns include intrinsic alterations and acquired resistance mechanisms (e.g. ESR1-mut). 
  • Elacestrant provides clinically meaningful improvements in PFS for patients with ER+/HER2- mBC who received at least 12 months of ET+CDK4/6i in 1st line and whose tumours harbour ESR1-mut. This benefit was consistent across clinically relevant subgroups. 
  • Safety analyses demonstrated that elacestrant had a manageable safety profile similar to other ETs and without evidence of some of the toxicities associated with other drug classes, such as CDK4/6i and PI3K/AKT/mTOR inhibitors.
  • ESR1-mut testing should be done at 1st line progression via liquid biopsy due to disease subclonality; if negative, repeat at each progression. Archival tissue should not be used for testing due to the acquired nature of ESR1-mut. 

Shaheenah Dawood is a Consultant medical oncologist and professor in clinical oncology in the United Arab Emirates. She trained in medical oncology at McGill University Hospitals in Canada and subspecialized in breast cancer management at MD Anderson Cancer Center. During her training she was awarded multiple scholar in training awards and ASCO merit awards. She has served as an editorial fellow at the New England Journal of medicine and has an MPH from the Harvard School of Public Health. She has over 100 papers to her credit including 50 peer review original articles, 30 review articles and 12 book chapters. She serves as a reviewer for multiple journals. She currently leads the oncology clinical trials program at Mediclinic City Hospital Dubai. She also serves as president of the Excellence in oncology summit that is held annually in Dubai and is co president of the Asia pacific breast cancer summit (ABCS) and Asia pacific gastrointestinal cancer summit (APGCS). She has also recently launched the international BRCA forum and young womens forum.

Prof. Shaheenah Dawood has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

MSD, Roche, BMS, New Bridge, Novartis, llilly , Pfizer, Caris, Merck, Jaansen, Ipsen,Astrazeneca, Zulleg Pharma

Professor of internal medicine at UT Southwestern Medical Center and a member of the Division of Hematology and Oncology. Clinical Director of the Breast Cancer Program at Simmons Cancer Center and specializes in breast cancer research and treatment.

Prof. Heather McArthur has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Amgen, AstraZeneca, BeiGene, Boston Scientific, Bristol-Myers Squibb, Calithera, Celgene, Daiichi-Sankyo, Delcath Systems Inc., Eli Lilly, Genentech/Roche, Gilead, Immunomedics, Merck, Moderna, Novartis, OBI Pharma, Peregrine, Pfizer/Seattle Genetics, Puma, Spectrum Pharmaceuticals, Stemline Therapeutics, Syndax Pharmaceuticals,TapImmune, Bristol-Myers Squibb, MedImmune, LLC/AstraZeneca; BTG; and Merck.

Head of the International Breast Cancer Centre (IBCC) in Barcelona, founding partner of Medica Scientia innovation Research (MedSIR), a company involved in the clinical development of clinical trials. Member of the Scientific Committee of the ESMO and EBCC.

Prof. Javier Cortés has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Roche , AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharp & Dohme, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Scorpion Therapeutics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, Abbvie, BridgeBio, Biontech, Biocon, Circle Pharma, Delcath Systems, Roche, Novartis, Eisai, Pfizer, Lilly, Merck Sharp & Dohme, Daiichi Sankyo, Astrazeneca, Gilead, Stemline Therapeutics.

Frédérique PENAULT-LLORCA, MD, PhD, graduated as a medical specialist in pathology in 1993 and in oncology in 1995. Also, in 1995, she received a PhD from the Université d’Aix-Marseille II in cellular biology and microbiology, on the topic of HER2. Frédérique PENAULT-LLORCA is currently professor of pathology at the University of Clermont-Ferrand, CEO of the Comprehensive Regional Cancer Institute Centre Jean PERRIN, Clermont-Ferrand, France, deputy director of the research team INSERM 1240 IMoST, and head of the Molecular Biology Plateform at Centre Jean Perrin. She serves as vice-president of the UNICANCER group and chairs of the Immuno-Oncology group at UNICANCER R&D. She is a member of several pathology and oncology societies, with her main areas of expertise being female cancers. She co-chairs the French breast cancer guidelines of Nice-St Paul. Frédérique PENAULT-LLORCA has conducted various biomarkers-based research studies in breast, lung, digestive tract, prostate and thyroid cancer in relation to response to targeted therapies and immunotherapies. Frédérique PENAULT-LLORCA has participated to more than 469 peer-reviewed publications and several books on female cancers and pathologic testing methods and issues.

Prof. Frédérique Penault-Llorca has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

AbbVie, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Genomic Health, Gilead, GSK, Lilly, Menarini /Stemline, MERCK, MSD, Myriad, NanoString Technologies, Novartis, Pfizer, Pierre-Fabre, Roche, Seagen, Servier, Tesaro; Institutional research grants from  AbbVie, Agendia, AstraZeneca, Bayer, BMS, Genomic Health, MSD, Myriad, NanoString Technologies, Roche; Congress invitations from AbbVie, AstraZeneca, BMS, MSD, Novartis, Pfizer, Roche 

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