HER2 Breast Cancer

The decision follows phase 3 trial results that demonstrated improved progression-free survival and confirmed the safety of Dato-DXd in patients with breast cancer.

Tucatinib significantly improved median PFS in the overall population and those with brain metastases.

pCR rates improve regardless of whether patients received full chemotherapy doses.

The combination resulted in numerically longer OS compared with an NSAI alone.

The candidate has already demonstrated anti-tumor activity in chemotherapy-naïve patients.

There is a prognostic impact of clinical and immunohistochemistry markers.

Douglas Warner, MD, chief medical officer at eFFECTOR, provides a comprehensive overview of zotatifin and its current status in a Phase 1/2 dose escalation and expansion study, with a focus on ER+/HER2- breast cancer.

Improvements in PFS were also seen among patients with brain metastases.

pCR rates were improved with the addition of pembrolizumab regardless of whether patients received the full chemotherapy doses.

MONARCH 3 final OS data show that the combination of abemaciclib and a NSAI in the first-line resulted in numerically longer OS compared to an NSAI alone.

Patients with an estrogen receptor measure greater than 8% and those with little to no TIL expression showed no benefit with the addition of nivolumab.

Although PFS was improved in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, OS data were immature, requiring further research.

With their final thoughts, the panelists provide key takeaways from their conversation regarding CDK4/6 inhibitor therapy in treatment of HR+/HER2- metastatic breast cancer.

Datopotamab deruxtecan (Dato-DXd; AstraZeneca, Daiichi Sankyo) also demonstrated improved overall survival compared to chemotherapy.

The combination regimen showed positive progression-free survival results among patients with HER2-positive breast cancer in the phase 3 HER2CLIMB-02 trial, but overall survival data have yet to mature.

There are currently no HER2-directed therapies for many HER2-expressing solid tumors that are refractory.

The trial was recommended to continue to analyze event-free survival rates, but current results are encouraging for treating estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.

Because of its prevalence in approximately 50% of breast cancers, the outcomes of HER2-low treatment have a significant impact on patient outcomes.

Trastuzumab deruxtecan was approved by the FDA for HER2-low breast cancer treatment in 2022 and could also benefit some patients with hormone receptor-positive or triple-negative disease.

Indication for abemaciclib (Verzenio; Eli Lilly and Company) in combination with endocrine therapy expanded for the adjuvant treatment of adults with hormone receptor–positive, human epidermal growth factor receptor 2-negative, node-positive, early breast cancer with a high risk of recurrence.

HER2-low disease demands a different approach from that of HER2-negative disease.

Sacituzumab govitecan-hziy (Trodelvy) is a conjugated Trop-2-directed antibody and topoisomerase inhibitor previously approved for patients with triple-negative breast cancer.

The FDA has approved elacestrant (Orserdu) for the treatment of postmenopausal women or adult men with estrogen receptor–positive (ER+), HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy.

This is the first indication for tucatinib that extends beyond the treatment of advanced unresectable or metastatic HER2-positive breast cancer.

Long-term data showed no difference in the clinical benefit between the treatments for HER2-negative early breast cancer with homologous recombination deficiency.