12 TIP HARMONIA SOLTI-2101/ AFT-58: A Head-to-Head Phase III Study Comparing Ribociclib (RIB) and Palbociclib (PAL) in Patients (pts) With Hormone Receptor– Positive/HER2-Negative/HER2- Enriched (HR+/HER2−/HER2-E) Advanced Breast Cancer (ABC)

Publication
Article
Miami Breast Cancer Conference® Abstracts Supplement40th Annual Miami Breast Cancer Conference® - Abstracts
Volume 37
Issue suppl 4
Pages: 16

Background

RIB and PAL are CDK4/6 inhibitors with efficacy and tolerability in pts with HR+/HER2− ABC when administered in combination with endocrine therapy (ET). RNA-based intrinsic subtyping has strong prognostic and predictive value in advanced HR+/HER2− tumors treated with ET. Nonluminal subtypes, such as HER2-E and basal-like, are relatively endocrine-resistant and have a poorer prognosis than luminal. Tumors can switch subtypes over time to more aggressive and less endocrine-responsive biology, which may also be reversed by effective treatment. A pooled retrospective analysis of MONALEESA 2/3/7 trials showed that HER2-E tumors had surprising benefits from RIB treatment, while basal-like tumors did not. Pre/clinical data suggest that RIB may outperform PAL in HER2-E. HARMONIA seeks to identify the best therapeutic option between RIB and PAL for pts with HR+/ HER2−/HER2-E ABC and aims to test whether RIB changes tumor biology thus enabling better response to ET and improving the disease course. In addition, it explores the value of earlier treatment with chemotherapy in pts with basal-like tumors.

Materials and Methods

This is an international, multicenter, randomized, open-label, phase 3 study, using prospective pre-selection based on tumor biology in pts with HR+ (ER <100%)/HER2– ABC, with HER2-E tumors (main cohort, 456 pts) and with basal-like tumors (exploratory cohort ~60 pts). Pts with HER2-E tumors will be randomized 1:1 to RIB+ET (letrozole or fulvestrant) or PAL+ET. In the basal-like cohort, pts will be treated with paclitaxel. Primary end point (EP): progression-free survival (PFS) per RECIST v1.1 by investigator-assessment. Secondary EP: overall survival, PFS2, clinical benefit rate, duration and time to response, quality of life, and exploratory EP, including subtype switching between primary and metastatic tumors, and after-trial treatment. Primary EP final analysis will be performed after 310 PFS events are observed (~80% power using one-sided 5% α).

Status

HARMONIA will recruit in Spain (40 sites), Portugal (5), and the US (35) within SOLTI & AFT network.

AFFILIATIONS:

Lisa Carey,1,2 Tomas Pascual,1,2 Daniel Stover,3 Astrid Thuerigen,4 Charles Perou,5 Eva Ciruelos,1,6 Ana Casas,1 Patty Spears,7 Estelle Roux,4 Faye Su,8 Hullin Hu,8 Yen-Shen Lu,9 Sara M. Tolaney,10 Ann Partridge,10 Guillermo Villacampa,11 Juan Manuel Ferrero-Cafiero,1 Aleix Prat1,2

1SOLTI Cancer Research Group, Barcelona Spain.

2Medical Oncology Department, Hospital Clinic de Barcelona, Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.

3Medical Oncology Department, Stefanie Spielman Comprehensive Breast Center, Columbus, OH.

4Novartis Pharma AG, Basel, Switzerland.

5Perou Lab, UNC – Lineberger Comprehensive Cancer Center, Chapel Hill, NC.

6Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.

7Lineberger Comprehensive Cancer Center, UNC - Lineberger Cancer Center, Chapel Hill, NC.

8Novartis Pharmaceuticals Corp., East Hanover, NJ.

9Department of Oncology, NTUH – National Taiwan University Hospital, Taipei City, Taiwan. 10Medical Oncology, Dana Farber Cancer Institute, Boston, MA.

11Statistics Department, Vall d’Hebron Institute of Oncology (VHIO)-Cellex Center, Barcelona, Spain.

12Alliance Breast Committee/UNC – Lineberger Comprehensive Cancer Center, Chapel Hill, NC.

Articles in this issue

1 Elacestrant Versus Fulvestrant or Aromatase Inhibitor in a Phase 3 Trial Evaluating Elacestrant, an Oral Selective Estrogen Receptor Degrader Versus Standard-of- Care Endocrine Monotherapy for ER+/HER2– Advanced/Metastatic Breast Cancer
1 Elacestrant Versus Fulvestrant or Aromatase Inhibitor in a Phase 3 Trial Evaluating Elacestrant, an Oral Selective Estrogen Receptor Degrader Versus Standard-of- Care Endocrine Monotherapy for ER+/HER2– Advanced/Metastatic Breast Cancer
2 Molecular Characterization of HER2-Low Patients Identifies Basal-Enriched Subset With Poor Clinical Outcomes in Real-world Data
2 Molecular Characterization of HER2-Low Patients Identifies Basal-Enriched Subset With Poor Clinical Outcomes in Real-world Data
3 Real-world Outcomes of Sacituzumab Govitecan in Metastatic Breast Cancer Patients: A Single Institution Experience
3 Real-world Outcomes of Sacituzumab Govitecan in Metastatic Breast Cancer Patients: A Single Institution Experience
4 Datopotamab Deruxtecan (Dato-DXd) + Durvalumab (D) as First-Line (1L) Treatment for Unresectable Locally Advanced/ Metastatic Triple-Negative Breast Cancer (a/mTNBC): Updated Results From BEGONIA, a Phase 1b/2 Study
4 Datopotamab Deruxtecan (Dato-DXd) + Durvalumab (D) as First-Line (1L) Treatment for Unresectable Locally Advanced/ Metastatic Triple-Negative Breast Cancer (a/mTNBC): Updated Results From BEGONIA, a Phase 1b/2 Study
5 Treatment Patterns and Clinical Outcomes in Patients Receiving Palbociclib Combinations as First- Line Treatment for Advanced or Metastatic Breast Cancer in Realworld Settings in Argentina and Colombia: Results from the IRIS Study
5 Treatment Patterns and Clinical Outcomes in Patients Receiving Palbociclib Combinations as First- Line Treatment for Advanced or Metastatic Breast Cancer in Realworld Settings in Argentina and Colombia: Results from the IRIS Study
7 EMERALD Phase 3 Trial of Elacestrant Versus Standard-of- Care Endocrine Therapy in Patients With ER+/HER2– Metastatic Breast Cancer: Updated Results by Duration of Prior CDK4/6i in Metastatic Setting
7 EMERALD Phase 3 Trial of Elacestrant Versus Standard-of- Care Endocrine Therapy in Patients With ER+/HER2– Metastatic Breast Cancer: Updated Results by Duration of Prior CDK4/6i in Metastatic Setting
8 Datopotamab Deruxtecan (Dato-DXd) in Advanced Triple- Negative Breast Cancer (TNBC): Updated Results From the Phase 1 TROPION-PanTumor01 Study
8 Datopotamab Deruxtecan (Dato-DXd) in Advanced Triple- Negative Breast Cancer (TNBC): Updated Results From the Phase 1 TROPION-PanTumor01 Study
9 Phase 1 TROPION-PanTumor01 Study Evaluating Datopotamab Deruxtecan (Dato-DXd) in Unresectable or Metastatic Hormone Receptor–Positive/ Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer
9 Phase 1 TROPION-PanTumor01 Study Evaluating Datopotamab Deruxtecan (Dato-DXd) in Unresectable or Metastatic Hormone Receptor–Positive/ Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer
11 Real-world Treatment Patterns and Effectiveness of Palbociclib Plus an Aromatase Inhibitor in Patients With Metastatic Breast Cancer Aged 75 Years or Above
11 Real-world Treatment Patterns and Effectiveness of Palbociclib Plus an Aromatase Inhibitor in Patients With Metastatic Breast Cancer Aged 75 Years or Above
12 TIP HARMONIA SOLTI-2101/ AFT-58: A Head-to-Head Phase III Study Comparing Ribociclib (RIB) and Palbociclib (PAL) in Patients (pts) With Hormone Receptor– Positive/HER2-Negative/HER2- Enriched (HR+/HER2−/HER2-E) Advanced Breast Cancer (ABC)
12 TIP HARMONIA SOLTI-2101/ AFT-58: A Head-to-Head Phase III Study Comparing Ribociclib (RIB) and Palbociclib (PAL) in Patients (pts) With Hormone Receptor– Positive/HER2-Negative/HER2- Enriched (HR+/HER2−/HER2-E) Advanced Breast Cancer (ABC)
13 Improved Sensitivity in Identification of ER- and HER2- Expressing Metastatic Breast Cancers With a Combination of Cell & Cell-Free Liquid Biopsy Analysis
13 Improved Sensitivity in Identification of ER- and HER2- Expressing Metastatic Breast Cancers With a Combination of Cell & Cell-Free Liquid Biopsy Analysis
15 Updated Expert Consensus Recommendations for Managing Hyperglycemia and Rash in Patients With PIK3CA-Mutated, Hormone Receptor–Positive (HR+), Human Epidermal Growth Factor Receptor 2–Negative (HER2–) Advanced Breast Cancer Treated With Alpelisib
15 Updated Expert Consensus Recommendations for Managing Hyperglycemia and Rash in Patients With PIK3CA-Mutated, Hormone Receptor–Positive (HR+), Human Epidermal Growth Factor Receptor 2–Negative (HER2–) Advanced Breast Cancer Treated With Alpelisib
16 Primary Results From the Randomized Phase II RIGHT Choice Trial of Premenopausal Patients With Aggressive HR+/HER2− Advanced Breast Cancer Treated With Ribociclib + Endocrine Therapy vs Physician’s Choice Combination Chemotherapy
16 Primary Results From the Randomized Phase II RIGHT Choice Trial of Premenopausal Patients With Aggressive HR+/HER2− Advanced Breast Cancer Treated With Ribociclib + Endocrine Therapy vs Physician’s Choice Combination Chemotherapy
17 A Clinical Systematic Literature Review of Treatments Among Patients With Advanced/ Metastatic HER2+ Breast Cancer
17 A Clinical Systematic Literature Review of Treatments Among Patients With Advanced/ Metastatic HER2+ Breast Cancer
20 TIP ELONA: An Open-Label, Phase 1b-2 Study of Elacestrant, in Combination With Onapristone in Patients With Estrogen Receptor– Positive, Progesterone Receptor– Positive, HER2-Negative Advanced or Metastatic Breast Cancer
20 TIP ELONA: An Open-Label, Phase 1b-2 Study of Elacestrant, in Combination With Onapristone in Patients With Estrogen Receptor– Positive, Progesterone Receptor– Positive, HER2-Negative Advanced or Metastatic Breast Cancer
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