Updates from ASCO 2024: Metastatic Breast Cancer

Educational Objectives

The goal of this program is to provide updates on the management of metastatic breast cancer. After hearing and assimilating this program, the clinician will be better able to:

1. Determine whether a patient with advanced breast cancer is likely to respond to fulvestrant.

Summary

postMONARCH (2022) primary outcome: phase 3 trial evaluated abemaciclib plus fulvestrant (FUL) vs FUL alone in HR+, HER2- advanced breast cancer (BC) patients who had progressed on prior cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy; CDK4/6 inhibitors with endocrine therapy is standard first-line treatment for HR+, HER2- advanced BC; abemaciclib — a CDK4/6 inhibitor; allows continuous dosing due to lower myelosuppression; approved in combination with aromatase inhibitors and FUL in metastatic settings and as monotherapy in high-risk early BC; shown to improve 6-mo progression-free survival (PFS) rate; takeaways — patient selection is critical in post-progression cases; biomarker-positive patients, particularly those with PIK3CA mutations, may benefit, though diabetes could complicate treatment decisions in some of these patients; patients with bone-only disease tend to respond better to FUL, while those with visceral metastasis may not benefit; patients who have remained on a prior CDK4/6 inhibitor for ≥12 mo may be suitable

Primary results from DESTINY-Breast 06 trial: evaluated trastuzumab deruxtecan (T-DXd) vs physician's choice of chemotherapy in HR+, HER2-low (IHC 1+ or 2+/ISH-) or ultralow (IHC 0 with membrane staining) metastatic BC after prior endocrine therapy; the primary endpoint was PFS in HER2-low and intent-to-treat arms (HER2-low and ultralow); in the HER2-low group, T-DXd extended median PFS from 8.1 to 13.2 mo compared with chemotherapy; intent-to-treat analysis showed similar results, with T-DXd having a PFS of 13.2 mo vs 8.1 mo for chemotherapy; overall survival (OS) data are not yet mature; subgroup analysis showed benefit across all groups; the overall response rate was 57% with T-DXd vs 31% with chemotherapy; common T-DXd side effects included nausea, fatigue, diarrhea, and pneumonitis (11%)

JBCRG-M06/EMERALD trial (Yamashita et al [2020]): investigated trastuzumab (H) and pertuzumab (P; HP) combined with eribulin mesylate (EM) vs a taxane as first-line treatment for HER2+ locally advanced or metastatic BC; patients, who were ≥6 mo post-neoadjuvant or adjuvant chemotherapy, were randomized 1:1 to EM-HP or taxane (docetaxel or paclitaxel) plus HP; the primary endpoint was PFS, and EM met the criteria for noninferiority, with a median PFS of 14 mo vs 12.9 mo in the taxane group; patients remained on EM longer than on taxanes; OS data for EM was not yet reached; peripheral neuropathy was higher in the EM arm than in the taxane arm; EM is noninferior to taxanes as a chemotherapy partner for HER2 dual blockade, but peripheral neuropathy remains a concern with its use

TBCRC 048 Expansion (Tung et al [2020]) cohorts: this phase 2 study evaluated olaparib monotherapy in metastatic BC patients with germline PALB2 (gPALB2) or somatic BRCA1/2 (sBRCA) mutations; while PARP inhibitors are approved for germline BRCA1/2, this study focused on other mutations, eg, gPALB2, sBRCA, ATM, and CHEK2; initial results showed an 82% overall response rate (ORR) for gPALB2 and 50% for sBRCA, leading to expansion cohorts with 30 patients each; gPALB2 had a 75% ORR, with responses across all subtypes, and a median PFS of 9.6 mo; for sBRCA, the ORR was 37%, with a median PFS of 7.2 mo; olaparib is recommended for gPALB2 patients regardless of BC subtype, while more data are needed to predict responses in sBRCA

Readings

Gradishar WJ, Moran MS, Abraham J, et al. NCCN Guidelines Insights: Breast Cancer, Version 4.2023. J Natl Compr Canc Netw. 2023 Jun;21(6):594-608. doi: 10.6004/jnccn.2023.0031; Kalinsky K, Accordino MK, Chiuzan C, et al. Randomized phase II trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: MAINTAIN Trial. J Clin Oncol. 2023 Aug 20;41(24):4004-4013. doi: 10.1200/JCO.22.02392; Kalinsky K, Layman RM, Kaufman PA, et al. postMONARCH: A phase 3 study of abemaciclib plus fulvestrant versus placebo plus fulvestrant in patients with HR+, HER2-, metastatic breast cancer following progression on a CDK4 & 6 inhibitor and endocrine therapy. JCO. 2022; 40:16_suppl, TPS1117-TPS1117. DOI:10.1200/JCO.2022.40.16_suppl.TPS1117; Sledge GW Jr, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: a randomized clinical trial. JAMA Oncol. 2020 Jan 1;6(1):116-124. doi: 10.1001/jamaoncol.2019.4782; Tung NM, Robson ME, Ventz S, et al. TBCRC 048: Phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes. J Clin Oncol. 2020 Dec 20;38(36):4274-4282. doi: 10.1200/JCO.20.02151; Walsh EM, Mangini N, Fetting J, et al. Olaparib use in patients with metastatic breast cancer harboring somatic BRCA1/2 mutations or mutations in Non-BRCA1/2, DNA damage repair genes. Clin Breast Cancer. 2022 Jun;22(4):319-325. doi: 10.1016/j.clbc.2021.12.007; Yamashita T, Masuda N, Saji S, et al. Trastuzumab, pertuzumab, and eribulin mesylate versus trastuzumab, pertuzumab, and a taxane as a first-line or second-line treatment for HER2-positive, locally advanced or metastatic breast cancer: study protocol for a randomized controlled, non-inferiority, phase III trial in Japan (JBCRG-M06/EMERALD). Trials. 2020 May 7;21(1):391. doi: 10.1186/s13063-020-04341-y. Erratum in: Trials. 2020 Jun 8;21(1):503. doi: 10.1186/s13063-020-04408-w. PMID: 32381018; PMCID: PMC7206765.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Yarlagadda was recorded at University of Chicago Annual Practice Updates in Hematology and Oncology, held on August 9, 2024, in Oak Brook, IL, and presented by the University of Chicago Pritzker School of Medicine. For information on upcoming CME activities from this presenter, please visit cme.uchicago.edu. Audio Digest thanks the speakers and the University of Chicago Pritzker School of Medicine for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

ON152304

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.