Trastuzumab-deruxtecan has been proven meaningfully superior to chemotherapy either in 1st and later lines after progression to CDK4/6i in HER2-low ABC and results with other ADCs as Sacituzumab Govitecan and Datopotamab-deruxtecan are promising, but the definition of cross-resistance between these drugs sharing either antibody or payload is crucial before implementing them in a useful sequence. On the other hand, the results obtained with immune checkpoint inhibitors (ICIs) in HR+/HER2-ABC contrarily to the early setting are disappointing up to now, but investigations of ICIs in combination with other targeted drugs which may increase immune response and the search for better markers of activity are under way. Moreover the anticipation in upfront treatment of ADCs or PARPi in patients with features of putative endocrine resistance and/or of less sensitiviy to CDK4/6i and the choice of therapy in patients recurring during or soon after adjuvant CDK4/6i and olaparib represent further challenges for the future.

1 month ago

Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PALB2 (Partner and localizer of BRCA2)

HER-2 positive • HR positive • HER-2 negative • PALB2 mutation • HR positive + HER-2 negative • HER-2 negative + HR positive + BRCA mutation

Lynparza (olaparib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Trodelvy (sacituzumab govitecan-hziy) • Datroway (datopotamab deruxtecan)

2ms

A Study of Olaparib and Pembrolizumab in People with Triple Negative Breast Cancer (TNBC) or Hormone Receptor-positive HER2-negative Breast Cancer (clinicaltrials.gov)

P2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

2 months ago

Enrollment closed

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • HR positive + HER-2 negative • RAD51 mutation • HER-2 negative + HR positive + BRCA mutation

Keytruda (pembrolizumab) • Lynparza (olaparib)

3ms

OptiTROP-Breast01: SKB264 Injection Vs Investigator Selected Regimens to Treat Locally Advanced, Recurrent or Metastatic Triple-negative Breast Cancer (clinicaltrials.gov)

P3, N=254, Active, not recruiting, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Trial completion date: Dec 2024 --> Mar 2025

3 months ago

Trial completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • HER-2 negative • HER-2 expression • PGR negative • HER-2 negative + HR positive + BRCA mutation

gemcitabine • capecitabine • Halaven (eribulin mesylate) • vinorelbine tartrate • sacituzumab tirumotecan (MK-2870)

4ms

Real-world demographics, clinical characteristics, and treatment patterns among US patients with HER2-negative early breast cancer and germline BRCA mutations since 2021 (SABCS 2024)

Pembrolizumab (n=92/151, 61%) and CT (n=54/151, 36%) were the most common neoadjuvant therapies for TNBC. Recently updated cancer guidelines endorse gBRCAm testing in all pts â‰¤65 years with a breast cancer diagnosis, pts >65 years who are candidates for PARP inhibitor therapy, and other high-risk individuals. This real-world analysis of pts diagnosed since 2021 showed that 55% of pts with HR+/HER2âˆ’ eBC and 27% with TNBC did not receive a gBRCA test, and utilization of adjuvant olaparib was low, particularly among pts with HR+/HER2âˆ’ eBC. Wider implementation of genetic testing is needed to ensure appropriate utilization of olaparib in eligible pts with eBC.

4 months ago

Real-world evidence • Clinical • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker • Real-world

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

HR positive • HER-2 negative • BRCA mutation • HER-2 negative + HR positive + BRCA mutation

Oncotype DX Breast Recurrence Score®Test

Keytruda (pembrolizumab) • Lynparza (olaparib)

4ms

BRCA1/2 alterations in circulating tumor DNA: correlation with germline origin and impact on survival in breast cancer. (SABCS 2024)

The VAF cut-off identified for the likelihood of a germinal mutation detected by ctDNA resulted lower than expected, underlining the importance of a larger germline BC screening, with considerable impact on therapeutic decision making and germline testing of other family members. Further analysis to explore the interplay of different co-mutations with BRCA1/2 will be performed and validation in additional dataset is needed.

4 months ago

PARP Biomarker • BRCA Biomarker • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

HER-2 positive • TP53 mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative • BRCA1 mutation + BRCA2 mutation • HER-2 negative + HR positive + BRCA mutation

Guardant360® CDx

5ms

CHANGEABLE: Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=37, Completed, Fudan University | Recruiting --> Completed

5 months ago

Trial completion • Metastases

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • PTEN mutation + HR positive • CHEK1 expression • HER-2 negative + HR positive + BRCA mutation

Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)