Consensus or Controversy? Documenting and Discussing Investigators’ Approaches to the Use of Oral SERDs and Agents Targeting the PI3K/AKT/mTOR Pathway in Breast Cancer

Faculty

Faculty

Sara A Hurvitz

MD, FACP

Fred Hutchinson Cancer Center, Seattle, Washington

Professor of Medicine, Smith Family Endowed Chair in Women’s Health, Senior Vice President, Clinical Research Division

UW Medicine, Seattle, Washington

Head, Division of Hematology/Oncology, Department of Medicine

Faculty

Erica Mayer

MD, MPH, FASCO

Dana-Farber Cancer Institute, Boston, Massachusetts

Director of Breast Cancer Clinical Research, Breast Oncology Center

Harvard Medical School, Boston, Massachusetts

Associate Professor of Medicine

Faculty

Joyce O’Shaughnessy

MD

Baylor University Medical Center Dallas, Texas

Celebrating Women Chair in Breast Cancer Research

Sarah Cannon Research Institute Dallas, Texas

Chair, Breast Disease Committee

Faculty

Nicholas Turner

MD, PhD

The Royal Marsden NHS Foundation Trust London, United Kingdom

Head, Ralph Lauren Centre for Breast Cancer Research Breast Unit Director, Clinical Research Director, The Royal Marsden and Institute of Cancer Research NIHR Biomedical Research Centre

Moderator

Sara M Tolaney

MD, MPH

Dana-Farber Cancer Institute, Boston, Massachusetts

Chief, Division of Breast Oncology

Harvard Medical School, Boston, Massachusetts

Associate Professor of Medicine

Program Schedule — Central Time
6:30 PM – 7:00 PM — Registration and Dinner
7:00 PM – 9:00 PM — Educational Meeting

MODULE 1: Current and Future Roles of Agents Targeting the PI3K/AKT/mTOR Pathway and Oral Selective Estrogen Receptor Degraders (SERDs) in First-Line Therapy for Hormone Receptor (HR)-Positive, HER2-Negative Metastatic Breast Cancer (mBC)

• Optimal approach to and timing of biomarker assessment for patients with HR-positive mBC; increasing relevance of biomarker evaluation in the up-front setting
• Key findings, including overall survival data, from the Phase III INAVO120 study evaluating inavolisib in combination with palbociclib and fulvestrant as first-line therapy for patients with HR-positive, HER2-negative mBC with a PIK3CA mutation whose disease progressed during or within 12 months of adjuvant endocrine therapy
• FDA approval of inavolisib/palbociclib/fulvestrant and clinical role in the treatment of newly diagnosed HR-positive, HER2-negative mBC with a PIK3CA mutation
• Design, eligibility criteria and key endpoints of the Phase III SERENA-6 study evaluating a switch from an aromatase inhibitor (AI) to camizestrant after detection of an emergent ESR1 mutation during first-line therapy for HR-positive, HER2-negative mBC
• Published findings from the SERENA-6 trial; potential role of serial ESR1 testing using circulating tumor DNA (ctDNA) and early therapeutic switching in the care of patients found to harbor mutations
• Ongoing Phase III trials evaluating PI3K/AKT/mTOR pathway inhibitors (eg, the INAVO123, CAPItello-292 and VIKTORIA-2 studies) and oral SERDs (eg, the SERENA-4 and persevERA studies) as a component of first-line therapy for patients with HR-positive, HER2-negative mBC; estimated completion dates

MODULE 2: Role of Oral SERD Monotherapy in the Treatment of Progressive HR-Positive, HER2-Negative mBC

• Structural and mechanistic similarities and differences between fulvestrant and approved and investigational oral SERDs; implications for antitumor activity, tolerability and ease of use
• Published efficacy and safety results from the Phase III EMERALD trial and real-world datasets evaluating elacestrant for pretreated HR-positive, HER2-negative mBC
• Updated efficacy results documented with imlunestrant monotherapy in the Phase III EMBER-3 study evaluating that agent alone or in combination with abemaciclib for patients with HR-positive, HER2-negative mBC pretreated with endocrine therapy with or without a CDK4/6 inhibitor
• FDA approvals of elacestrant and imlunestrant for previously treated HR-positive, HER2-negative, ESR1-mutated mBC; optimal incorporation into management algorithms
• Available findings with other oral SERDs, such as camizestrant and giredestrant, administered as monotherapy for advanced HR-positive, HER2-negative breast cancer

MODULE 3: Potential Use of Oral SERD-Containing Combination Regimens in Managing Progressive HR-Positive, HER2-Negative mBC

• Biological rationale for combining oral SERDs with other systemic therapies for HR-positive mBC
• Updated efficacy and safety outcomes documented in the imlunestrant/abemaciclib arm of the EMBER-3 trial among patients with and without ESR1 mutations
• Indications, if any, for the nonresearch use of imlunestrant in combination with abemaciclib for endocrine therapy-pretreated, HR-positive, HER2-positive mBC
• Presented data from the Phase III evERA study of giredestrant in combination with everolimus versus standard endocrine therapy in combination with everolimus for pretreated HR-positive, HER2-negative mBC
• Potential clinical role of giredestrant/everolimus for previously treated HR-positive, HER2-positive mBC
• Early-phase data with and ongoing evaluation of other oral SERD-containing combination strategies for progressive HR-positive, HER2-negative mBC

MODULE 4: Clinical Utility of Agents Targeting the PI3K/AKT/mTOR Pathway for Patients with Progressive HR-Positive, HER2-Negative mBC

• Key efficacy and safety data from the Phase III CAPItello-291 study evaluating capivasertib/fulvestrant for HR-positive, HER2-negative mBC progressing on endocrine therapy with or without a CDK4/6 inhibitor
• FDA approval of capivasertib for patients with PIK3CA/AKT1/PTEN alterations and current therapeutic role with regard to other evidence-based options
• Mechanistic similarities and differences between gedatolisib and currently approved therapies targeting the PI3K/AKT/mTOR pathway in HR-positive mBC; implications for antitumor activity
• Design, eligibility criteria and primary and secondary endpoints of the Phase III VIKTORIA-1 trial evaluating gedatolisib in combination with fulvestrant with or without palbociclib for patients with HR-positive, HER2-negative advanced breast cancer whose disease progressed on or after prior CDK4/6 inhibitor therapy and an AI
• Recently published efficacy and safety findings from the PIK3CA wild-type cohort of VIKTORIA-1; anticipated readout of the PIK3CA-mutated cohort
• Potential role of gedatolisib-containing combination therapy for pretreated HR-positive, HER2-negative mBC that is PIK3CA wild type and PIK3CA mutated

MODULE 5: Potential Use of Oral SERDs for HR-Positive, HER2-Negative Localized BCr

• Rationale for the investigation of oral SERDs as adjuvant therapy for patients with HR-positive, HER2-negative localized breast cancer
• Design, eligibility criteria and primary and second endpoints of the Phase III lidERA Breast Cancer study evaluating adjuvant giredestrant versus physician’s choice of adjuvant endocrine monotherapy for patients with HR-positive, HER2-negative localized breast cancer
• Improvement in invasive disease-free survival and other key efficacy outcomes documented with adjuvant giredestrant in the lidERA Breast Cancer trial
• Tolerability profile of giredestrant versus standard adjuvant endocrine therapy in the lidERA Breast Cancertrial
• Potential clinical role of adjuvant giredestrant for patients with HR-positive, HER2-negative localized breast cancer
• Early data with and ongoing Phase III trials (eg, the ELEGANT, TREAT ctDNA, EMBER-4, CAMBRIA-1 and CAMBRIA-2 studies) of other oral SERDs in the adjuvant setting

Target Audience
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of lung cancer.

Learning Objectives
Upon completion of this activity, participants should be able to

• Appreciate the incidence and clinical implications of ESR1 mutations in endocrine-resistant metastatic breast cancer (mBC), and determine optimal strategies to effectively identify patients harboring these abnormalities.
• Understand the biological rationale for, mechanism of action of and pharmacologic similarities and differences among available and investigational oral selective estrogen receptor degraders (SERDs).
• Interrogate published research documenting the efficacy of oral SERD monotherapy for ER-positive, HER2-negative, ESR1-mutated mBC progressing on standard endocrine therapy in combination with a CDK4/6 inhibitor in order to optimally integrate these agents into the care of appropriately selected patients.
• Review available research data evaluating the role of serial ESR1 testing using circulating tumor DNA in informing early therapeutic switching for patients with ER-positive mBC receiving CDK4/6 inhibitor-based first-line therapy, and consider the potential role of this novel strategy.
• Evaluate available clinical trial data with oral SERDs in combination with other systemic therapies (eg, CDK4/6 inhibitors, mTOR inhibitors), and consider the potential role of these regimens.
• Recognize the frequency of PIK3CA/AKT/PTEN alterations in patients with hormone receptor (HR)-positive mBC, and employ evidence-based approaches to target these aberrations for appropriate candidates with newly diagnosed and relapsed/refractory disease.
• Understand the biological rationale for the development of agents targeting multiple components of the PI3K/AKT/mTOR pathway, and recognize available data employing this strategy for patients with HR-positive, PIK3CA wild-type and PIK3CA-mutant mBC.
• Appreciate side effects associated with available and investigational oral SERDs and other agents targeting the PI3K/AKT/mTOR pathway, and use this information to develop supportive care plans for patients receiving these treatments.
• Assess ongoing clinical research studies evaluating novel applications of oral SERDs and PI3K/AKT/mTOR inhibitor-based approaches, and counsel patients regarding the potential benefits of trial participation.

CME Credit Form
A CME credit link will be given to each participant as part of the meeting course materials.

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Dr Hurvitz — Advisory Committees: Akari Therapeutics, BeOne, Boundless Bio, BriaCell, BridgeBio, Bristol Myers Squibb, Daiichi Sankyo Inc, Gilead Sciences Inc, Jazz Pharmaceuticals Inc, Lilly, Luminate, Mersana Therapeutics Inc, Novartis, Prelude Therapeutics, Roche Laboratories Inc; Consulting Agreements: ALX Oncology, Bayer HealthCare Pharmaceuticals, BeOne, Blueprint Medicines, Ellipses Pharma, EMBioSys, Genentech, a member of the Roche Group, Jazz Pharmaceuticals Inc, Myricx Bio; Contracted Research: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Menarini Group, Novartis, Stemline Therapeutics Inc; Data and Safety Monitoring Boards/Committees: Atossa Therapeutics (paid to institution), Roche Laboratories Inc (paid to UW); Nonrelevant Financial Relationships: Alliance for Clinical Trials in Oncology Foundation, InClin, Quantum Leap Healthcare Collaborative, ROMTech (Stocks for orthopedic device for postop pts; not cancer related) Dr Mayer — Consulting Agreements: Aktis Oncology, AstraZeneca Pharmaceuticals LP, Genentech, a member of the Roche Group, Lilly, Novartis. Dr O’Shaughnessy — Advisory Committees and Consulting Agreements: Aadi Bioscience, Agendia Inc, Amgen Inc, Aptitude Health, AstraZeneca Pharmaceuticals LP, BioNTech SE, Bristol Myers Squibb, Daiichi Sankyo Inc, Duality Biologics, Eisai Inc, Ellipses Pharma, Exact Sciences Corporation, G1 Therapeutics Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Guardant Health, HiberCell, Jazz Pharmaceuticals Inc, Johnson & Johnson, Lilly, Menarini Group, Merck, Mersana Therapeutics Inc, Natera Inc, Novartis, Pfizer Inc, Pierre Fabre, Puma Biotechnology Inc, RayzeBio, Roche Laboratories Inc, Sanofi, Seagen Inc, Stemline Therapeutics Inc, Summit Therapeutics, Tempus, TerSera Therapeutics LLC. Dr Tolaney — Consulting Agreements: Aadi Bioscience, Ambrx, Artios Pharma Limited, Arvinas, AstraZeneca Pharmaceuticals LP, Aktis Oncology, Avenzo Therapeutics, Bayer HealthCare Pharmaceuticals, BeOne, Bicycle Therapeutics, BioNTech SE, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Boundless Bio, Bristol Myers Squibb, Celcuity, Circle Pharma, Cullinan Therapeutics, Daiichi Sankyo Inc, Denali Therapeutics, eFFECTOR Therapeutics Inc, Eisai Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Hengrui Therapeutics Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Launch Therapeutics, Lilly, Menarini Group, Merck, Mersana Therapeutics Inc, Natera Inc, Novartis, Olema Oncology, Pfizer Inc, Reveal Genomics, Samsung Bioepis, Seagen Inc, Stemline Therapeutics Inc, Sumitovant Biopharma, Summit Therapeutics, SystImmune Inc, Tango Therapeutics, Tempus, Zuellig Pharma; Contracted Research: AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Daiichi Sankyo Inc, Exelixis Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Jazz Pharmaceuticals Inc, Lilly, Menarini Group, Merck, NanoString Technologies, Novartis, OncoPep, Pfizer Inc, Seagen Inc, Stemline Therapeutics Inc; Travel: Arvinas, AstraZeneca Pharmaceuticals LP, Gilead Sciences Inc, Jazz Pharmaceuticals Inc, Lilly, Pfizer Inc, Roche Laboratories Inc.

MODERATOR
To be announced.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Summit Therapeutics, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

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Supporters
This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP, Celcuity, Genentech, a member of the Roche Group, Lilly, and Stemline Therapeutics Inc.

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