General Session 3 (available abstracts)

Publication Number: GS3-01

Trastuzumab deruxtecan (T-DXd; DS-8201a) vs. trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): subgroup analyses from the randomized phase 3 study DESTINY- Breast03

Sara Hurvitz, Sung-Bae Kim, Wei-Pang Chung, et al.

DESTINY-Breast03 is the first reported randomized phase 3 study comparing T-DXd with standard of care treatment. It met the primary endpoint and T-DXd demonstrated superior PFS over T-DM1 and T-DXd with a manageable safety profile. A consistent PFS and ORR benefit with T-DXd vs. T-DM1 was seen in all HER2 + metastatic breast cancer subgroups previously treated with trastuzumab and taxane, including patients with brain metastases.


Publication Number: GS3-03

Genomic analysis of 733 HER2+ breast cancers identifies recurrent pathways alterations associated with anti-HER2 resistance and new therapeutic vulnerabilities

Emanuela Ferraro, Alison Smith, Anton Safonov, et al.

PIK3CA-activating mutations detected by tumor sequencing and the lack of genomic ERBB2 amplification are associated with reduced progression-free survival in HP-based therapy. Our clinical-genomic analysis of the mechanisms of resistance clearly identified changes in the MAPK signaling pathway as additional potential drivers of resistance to anti-HER2 therapy. The authors speculate that inhibiting the PI3K or MAPK signaling pathway in such tumors could be a new therapeutic strategy to expand the H / P utility.


Publication Number: GS3-07

Circulating tumor DNA (ctDNA) dynamics in patients with hormone receptor positive (HR+)/HER2 negative (HER2-) advanced breast cancer (aBC) treated in first line with ribociclib (R) and letrozole (L) in the BioItaLEE trial

Giampaolo Bianchini, Luca Malorni, Grazia Arpino, et al.

Detectable mutations in liquid biopsies at the start of the study seem to be prognostic negative. VAF early clearance during the first ribociclib / letrozole cycle was informative in this high-risk group of treatment benefit and associated with a lower risk of progression. The monitoring of the ctDNA in patients without baseline mutations showed that the detection of new mutations by FI assessment is associated with a poor outcome. The pretreatment and early dynamics of the ctDNA (assessed by NGS) are promising prognostic and predictive biomarkers in patients with HR + / HER2-aBC treated first-line with ribociclib / letrozole.


Publication Number: GS3-09

Loss of ASXL1 tumor suppressor promotes resistance to CDK4/6 inhibitors in ER+ breast cancer

Dhivya R. Sudhan, Sumanta Chatterjee, Jiwoong Kim, et al.

CDK2 inhibitors can be a treatment approach for drug-resistant tumors. For more information please consult the abstract.


Publication Number: GS3-10

Study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in combination with fulvestrant in patients with advanced hormone receptor positive HER2 negative breast cancer (HR+BC)

Charles Coombes, Sasha J Howell, Matthew G Krebs, et al.

Samuraciclib plus fulvestrant shows an acceptable safety profile with evidence of anti-tumor activity in advanced HR + BC after previous CDK4 / 6i therapy.