Year in Review: Clinical Investigator Perspectives on the Most Relevant New Datasets and Advances Involving the PI3K/AKT/mTOR Pathway in HR-Positive Metastatic Breast Cancer — Webinar Proceedings

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, breast surgeons, radiation oncologists and other healthcare professionals involved in the diagnosis and treatment of breast cancer.

LEARNING OBJECTIVES

• Review available research documenting the correlation between the presence of various biomarkers (eg, PIK3CA/AKT1/PTEN alterations, ESR1 mutations) and response to specific therapies, and develop optimal testing algorithms for patients with hormone receptor (HR)-positive metastatic breast cancer (mBC).
• Recognize the frequency of PIK3CA/AKT1/PTEN alterations in patients with HR-positive mBC, and employ evidence-based approaches designed to target these aberrations as appropriate for those 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 with this strategy for patients with HR-positive, PIK3CA wild-type and PIK3CA-mutant mBC.
• Evaluate available research findings with and ongoing studies evaluating novel PI3K/AKT/mTOR inhibitor-based approaches, and consider the potential role of these strategies in clinical practice.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Research To Practice designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 1.25 Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, this program has been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, this program has been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
To receive credit for this activity, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better, and fill out the evaluation.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Dr Kaklamani — Consulting Agreements: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Menarini Group, Novartis, Pfizer Inc; Speakers Bureaus: AstraZeneca Pharmaceuticals LP, Gilead Sciences Inc. Dr Rugo — Consulting Agreements: BioNTech SE, Bristol Myers Squibb, Helsinn Therapeutics (US) Inc, Napo Pharmaceuticals; Contracted Research: Ambrx, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Merck, Novartis, Pfizer Inc, Stemline Therapeutics Inc; Research Funding (to Institution): ALX Oncology, Bicycle Therapeutics, Genentech, a member of the Roche Group, Mabwell Therapeutics Inc, Merck, Pfizer Inc, Phoenix Molecular Designs, Relay Therapeutics, Stemline Therapeutics Inc.

MODERATOR — 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, Catalyst Pharmaceuticals Inc, 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, Tesaro, A GSK Company, and Verastem Inc.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP and Celcuity.

Release date: August 2026
Expiration date: August 2027

Dr Kaklamani
Basho R et al. INAVO123: Phase 3 study of first-line inavolisib / placebo + a cyclin-dependent kinase 4/6 inhibitor + letrozole in participants with PIK3CA-mutated, hormone receptor-positive, HER2-negative, endocrine-sensitive advanced breast cancer. San Antonio Breast Cancer Symposium 2025;Abstract PS5-07-27.

Fernando S et al. PIK3R1 (p85α) alterations define a targetable subset of breast cancer with broad sensitivity to PI3K and AKT inhibitors. San Antonio Breast Cancer Symposium 2025;Abstract RF4-05.

Hilz S et al. Molecular features of response to palbociclib + fulvestrant ± inavolisib in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer as assessed from baseline circulating tumor DNA in the pivotal phase 3 INAVO120 trial. San Antonio Breast Cancer Symposium 2025;Abstract PD5-09.

Jhaveri KL et al. Overall survival with inavolisib in PIK3CA-mutated advanced breast cancer. N Engl J Med 2025;393(2):151-61. Abstract

Kalinsky K et al. Comparative analysis of blood- and tissue-based PIK3CA mutation detection methods in the pivotal phase 3 INAVO120 trial of palbociclib + fulvestrant ± inavolisib in hormone receptor-positive, HER2-negative advanced breast cancer. San Antonio Breast Cancer Symposium 2025;Abstract PS1-10-26.

Loibl S et al. Efficacy of inavolisib (INAVO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2-negative (HER2-), endocrine-resistant advanced breast cancer (aBC) with and without hyperglycaemia (HG) in the phase III INAVO120 trial. ESMO Breast Cancer 2026;Abstract 420RO.

Neven P et al. Capivasertib (C) + ribociclib (R) + fulvestrant (F) in patients (pts) with HR-positive/HER2-negative advanced breast cancer (ABC): CAPItello-292 phase Ib. ESMO Breast Cancer 2025;Abstract 316P.

Sudhan DR et al. Mechanisms of resistance to capivasertib in combination with CDK4/6 inhibitor (CDK4/6i) plus fulvestrant in patients with hormone receptor-positive/HER2-negative (HR+/HER2−) advanced breast cancer (ABC): Exploratory analysis from the phase 1b CAPItello-292 study. San Antonio Breast Cancer Symposium 2025;Abstract RF4-04.

Wesolowski R et al. Gedatolisib combined with palbociclib and letrozole in patients with no prior systemic therapy for hormone receptor-positive, HER2-negative advanced breast cancer. Clin Cancer Res 2025;31(19):4040-8. Abstract

Dr Rugo
Hurvitz SA et al. A randomized, open-label, phase 3 study of gedatolisib + fulvestrant ± palbociclib vs standard of care in HR+/HER2−/PIK3CA-mutant (MT) advanced breast cancer (VIKTORIA-1 Study 2). ASCO 2026;Abstract LBA1008.

Jhaveri KL et al. A phase 1/2 trial of tersolisib (LY4064809/STX-478), a pan-mutant-selective PI3Kα inhibitor (PI3Kαi), in PIK3CA-mutant advanced solid tumors: Updated results from PIKALO-1. ASCO 2026;Abstract 1072.

Pistilli B et al. Gedatolisib (Geda), a multitarget PI3K/AKT/mTOR (PAM) inhibitor, plus fulvestrant (Fulv) ± palbociclib (Palbo) for second-line (2L) treatment of patients (Pts) with HR+/HER2-/PIK3CA-wild type (WT) advanced breast cancer (ABC): Updated results from VIKTORIA-1. ESMO Breast Cancer 2026;Abstract 505P.

Rugo HS et al. Capivasertib (C) and fulvestrant (F) for patients (pts) with HR+/HER2- advanced breast cancer (ABC): Final overall survival (OS) results from the phase III CAPItello-291 trial. ESMO Breast Cancer 2026;Abstract 417O.

Rugo HS et al. Capivasertib plus fulvestrant as first and second-line endocrine-based therapy in PIK3CA/AKT1/PTEN-altered hormone receptor-positive advanced breast cancer: Subgroup analysis from the phase 3 CAPItello-291 trial. ESMO 2025;Abstract 526P.

Saura C et al. Efficacy of mutant-selective PI3Kα inhibitor RLY-2608 in combination with fulvestrant in patient (pt) subset populations, including pts with PIK3CA-mutant HR+/HER2- advanced breast cancer (BC) pre-treated with fulvestrant or other SERD. San Antonio Breast Cancer Symposium 2025;Abstract PD10-07.

Turner NC et al. Capivasertib plus fulvestrant in hormone receptor-positive (HR+) advanced breast cancer (ABC): Exploratory ctDNA analyses from the phase 3 CAPItello-291 trial. San Antonio Breast Cancer Symposium 2025;Abstract RF7-05.

Vaklavas C et al. Camizestrant in combination with capivasertib for women with ER-positive, HER2-negative advanced breast cancer: Results from SERENA-1. ESMO Open 2026;11(2):106049. Abstract