Findings from two phase 3 trials were presented during the first General Session on Wednesday at the 2023 SABCS®. The session is available on demand for registered SABCS^® participants through March 31, 2024, on the meeting platform. 

GS01-10 – HER2CLIMB-02: Randomized, double-blind phase 3 trial of tucatinib and trastuzumab emtansine for previously treated HER2-positive metastatic breast cancer

Findings from the phase 3 HER2CLIMB-02 trial presented at the 2023 SABCS® on Wednesday morning suggest that a combination of two HER2-targeted drugs—tucatinib and trastuzumab emtansine (T-DM1)—may extend progression-free survival (PFS) among patients with unresectable locally advanced or metastatic HER2-positive breast cancer, compared with T-DM1 alone.

The findings were reported during General Session 1 by Sara Hurvitz, MD, FACP, Professor and Head of the Division of Hematology and Oncology at the University of Washington Department of Medicine and Senior Vice President and Director of the Clinical Research Division at Fred Hutchinson Cancer Center. More information on the presentation is available here.

This study, Dr. Hurvitz said, is based on the results of the HER2CLIMB trial, which demonstrated that progression-free survival and overall survival, as well as progression-free survival in patients with brain metastases, was significantly improved by adding tucatinib to trastuzumab and capecitabine.

“The incidence of brain metastases in patients with HER2-positive advanced disease is quite high, some would indicate up to 50 percent,” Dr. Hurvitz said. “Both preclinical and phase 1/2 clinical trial data have indicated that the combination of TDM-1 with tucatinib has promising clinical activity and anti-tumor responses, as well as a manageable safety profile.”

In HER2CLIMB-02, patients were eligible for enrollment in the trial if they had HER2-positive locally advanced unresectable or metastatic breast cancer that progressed after trastuzumab and a taxane in any setting. Patients were also allowed if they had previously treated stable, progressing, or untreated brain metastases not requiring immediate local therapy.

“Approximately 460 patients were randomly assigned one-to-one to TDM-1 with tucatinib or TDM-1 with placebo,” Dr. Hurvitz said. “It is notable that about 44% of patients enrolled in this study had brain metastases, and about half of these patients had active brain metastases.”

Among the findings, Dr. Hurvitz reported that the median time to disease progression or death was 9.5 months for patients in the tucatinib arm and 7.4 months for patients in the placebo arm (HR=0.76), with tucatinib plus T-DM1 reducing the risk of disease progression or death by 24.1%. The hazard ratios for subgroups, she noted, were consistent with that of the overall population and the PFS for patients with brain metastases trended in favor of the tucatinib arm.

Additionally, in patients who had brain metastases at baseline, the investigators found that the median time to disease progression or death was 7.8 months for those in the tucatinib arm and 5.7 months for those treated in the placebo arm, with tucatinib plus T-DM1 reducing the risk of disease progression or death by 36.1%.

“Overall survival data are immature, and the types of adverse events were consistent with previous reporting,” Dr. Hurvitz said. “This is now the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting.”

GS01-13 – MONARCH 3: Final overall survival results of abemaciclib plus a nonsteroidal aromatase inhibitor as first-line therapy for HR+, HER2- advanced breast cancer

The final overall survival results from MONARCH 3 were presented as a late-breaking abstract on Wednesday at the 2023 SABCS®.

Matthew P. Goetz, MD, Professor of Oncology and Pharmacology, Department of Oncology
at Mayo Clinic, presented the results during General Session 1. More information on the presentation can be found here.

MONARCH 3 is a phase 3, randomized, double-blind study that evaluated the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as a first-line treatment in postmenopausal women with HR+, HER2- advanced breast cancer.

“The addition of abemaciclib to an NSAI as an initial therapy resulted in significant improvement in PFS and led to its global regulatory approval,” said Dr. Goetz. “In this final analysis, abemaciclib in combination with an NSAI resulted in longer OS compared to an NSAI alone; however this did not meet statistical significance.”

Prior analyses had shown that the addition of abemaciclib significantly improved progression-free survival (PFS) (hazard ratio (HR), 0.540; 95% confidence interval (CI), 0.418–0.698; p=0.000002) with a numerically favorable, non-significant improvement in overall survival (OS).

In this recent analysis, with 8.1 years of follow-up, median OS was 66.8 months in the abemaciclib + NSAI group and 53.7 months in the NSAI alone group (HR, 0.804; 95% CI, 0.637–1.015; p=0.0664).

Updated PFS results continue to show a robust benefit, with 23.3% of patients in the abemaciclib + NSAI group remaining progression free at 6 years, compared to 4.3% of patients in the NSAI alone group.

“Given this clinically meaningful, though non-significant, improvement in median OS and the sustained improvement in PFS, this final analysis of MONARCH 3 continues to support the use of abemaciclib in combination with an NSAI in the first-line setting,” Dr. Goetz concluded.

Following are all the abstracts presented during General Session 1:

• GS01-01: Biomarker Results in High-risk Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Primary Breast Cancer Following Neoadjuvant Chemotherapy ± Nivolumab: An Exploratory Analysis of CheckMate 7FL
• GS01-02: Phase 3 study of neoadjuvant pembrolizumab or placebo plus chemotherapy, followed by adjuvant pembrolizumab or placebo plus endocrine therapy for early-stage high-risk ER+/HER2− breast cancer: KEYNOTE-756
• GS01-03: Adding atezolizumab to adjuvant chemotherapy for stage II and III triple-negative breast cancer is unlikely to improve efficacy: interim analysis of the ALEXANDRA/IMpassion030 phase 3 trial.
• GS01-05: Pembrolizumab + Olaparib vs Pembrolizumab + Chemotherapy After Induction With Pembrolizumab + Chemotherapy for Locally Recurrent Inoperable or Metastatic TNBC: Randomized Open-Label Phase 2 KEYLYNK-009 Study
• GS01-06: Advancing Evidence of the Associations Between Specific Benign Breast Diagnoses and Future Breast Cancer Risk
• GS01-08: CDK4/6 inhibition is a potential vulnerability in NF1-depleted ER+ breast cancer
• GS01-10: HER2CLIMB-02: Randomized, Double-Blind Phase 3 Trial of Tucatinib and Trastuzumab Emtansine for Previously Treated HER2-Positive Metastatic Breast Cancer
• GS01-12: MONARCH 3: Final overall survival results of abemaciclib plus a nonsteroidal aromatase inhibitor as first-line therapy for HR+, HER2- advanced breast cancer