What’s New in Breast Cancer

Pumitamig: An investigational bispecific drug for metastatic triple-negative breast cancer

The ROSETTA-Breast01 trial is an ongoing study evaluating pumitamig in combination with chemotherapy for PD-L1-negative metastatic triple-negative breast cancer (TNBC). Pumitamig is a bispecific antibody, a type of immunotherapy that targets the proteins PD-L1 and VEGF-A. By targeting PD-L1, pumitamig helps the immune system recognize cancer cells. Simultaneously, the drug targets VEGF-A to keep blood vessels from forming, which starves cancer cells of the nutrients and oxygen needed for growth and survival. If approved, this could establish a new immunotherapy for PD-L1-negative metastatic TNBC.

Learn more in this clip from our Breast Cancer Breakthroughs series.

Giredestrant: An investigational oral SERD for early‑stage hormone receptor‑positive breast cancer

Giredestrant is an oral selective estrogen receptor degrader (SERD), a type of hormone therapy that works by breaking down the estrogen receptor in hormone receptor-positive (HR+) breast cancer cells. In the phase 3 lidERA trial, giredestrant improved disease-free survival compared with standard hormone therapy. If approved, it could become a new oral hormone therapy option for some people with early-stage HR+/HER2-negative (HER2-) breast cancer and mark the first oral SERD to benefit people with early breast cancer.

Izalontamab brengitecan: An investigational antibody-drug conjugate for metastatic triple-negative breast cancer

Izalontamab brengitecan (iza-bren) is a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3 to reduce cancer cell proliferation and survival signals, leading to cancer cell death by inducing stress in cancer cells. In the phase 3 PANKU-Breast-02 trial, iza-bren significantly improved overall and progression-free survival compared to chemotherapy in metastatic TNBC.

Read more about the results of this trial here.

New and improved technologies may be able to increase the speed and accuracy of detecting, diagnosing or monitoring breast cancer for progression and response to treatment.  

Interventions for early breast cancer

Women with high-risk, early HR+/HER2- breast cancer often receive chemotherapy to reduce the risk of cancer returning. The phase 3 OPTIMA trial used a genomic test called Prosigna to analyze the activity of 50 genes and assess a patient’s risk of recurrence. In the trial, Prosigna test results were used to guide chemotherapy decisions, allowing about seven out of 10 patients to safely avoid chemotherapy. Avoiding chemotherapy can reduce treatment-related toxicity and other treatment side effects, leading to a better quality of life for these patients.

Read more about the trial results here.

ctDNA & MRD testing: Expanding applications and new trials

The use of circulating tumor DNA (ctDNA) and minimal residual disease (MRD) testing is expanding across cancer research and care, including in breast cancer. New clinical trials continue to explore applications for ctDNA in breast cancer care such as detecting recurrence, helping inform potential treatment decisions in specific scenarios and monitoring treatment responses – though limitations in sensitivity, standardization and clinical value remain. Importantly, routine MRD-guided care is currently not included in the National Comprehensive Cancer Network’s (NCCN) Clinical Practice Guildelines in oncology for most patients, and the recent update to the American Society for Clinical Oncology (ASCO) Guidelines indicate that MRD testing is not yet considered a standard of care. The CATE clinical trial is one new trial aiming to use MRD testing to proactively identify early-stage HR+/HER2- breast cancers at high risk of recurrence, and adjust treatment based on that risk.

Read more about the CATE clinical trial here.

Artificial Intelligence (AI)-based risk assessment tool

Predicting one’s risk for developing breast cancer currently relies on several different factors including a person’s gender, age, ethnicity, reproductive history, health background and family health history. A new AI-based risk-assessment technology was recently granted authorization from the FDA. While the FDA has previously approved AI tools to assist in breast cancer detection and risk management, this is the first to receive authorization specifically for predicting five-year risk directly from a screening mammogram. However, the use of AI to provide additional information about someone’s breast cancer risk from mammograms is still being studied and is not yet part of standard screening care for most people.

With knowledge gained from clinical trials, researchers are seeking new ways to improve patient outcomes while using existing drugs. Some new breast cancer treatment breakthroughs are the result of combining certain drugs, finding which patients can skip certain elements of treatment or changing the order of their treatments to maximize effectiveness or to minimize side effects.

Trastuzumab deruxtecan (T-DXd) shifting earlier in HER2+ breast cancer treatment

Several DESTINY-Breast clinical trials have tested if T-DXd (an antibody-drug conjugate or ADC) is effective when used earlier in the treatment of HER2+ breast cancer.

• DESTINY-Breast05 demonstrated that T-DXd improved outcomes for people with high-risk residual HER2+ early breast cancer following neoadjuvant therapy compared to ado-trastuzumab emtansine (T-DM1) (an ADC). This is now FDA-approved in this setting.
• Destiny-Breast11 showed that when T-DXd was used as part of neoadjuvant therapy, it led to a higher pathologic complete response rate compared to chemotherapy-based approaches in HER2+ early breast cancer. This is now FDA-approved in this setting.
• DESTINY-Breast09 also evaluated T-DXd as a first-line option for HER2+ MBC and is now FDA-approved in combination with pertuzumab in this setting.

Together these trial results could shift how (and, more so, when) ADC’s might be used not only in metastatic disease but also earlier in the course of HER2+ breast cancer treatment.

To learn more about antibody drug conjugates, check out this video from our Under the Microscope video series.

TROP2-targeting antibody drug conjugates (ADCs) become a first‑line option for some metastatic triple-negative breast cancers(TNBC)

The results of recent trials are impacting how doctors treat metastatic TNBC – particularly for people who cannot receive immunotherapy. ADCs like sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) have shown they can help people live longer without disease progression compared to standard chemotherapy in first-line metastatic TNBC based on the TROPION-Breast02, ASCENT-03 and ASCENT-04 clinical trials.

SG is FDA-approved as a first-line treatment for metastatic TNBC either as a monotherapy or in combination with pembrolizumab (an immunotherapy drug). Dato-DXd is FDA-approved as first-line treatment for metastatic TNBC. The NCCN guidelines also list SG and Dato-DXd among the recommended first-line treatment options for certain people with metastatic disease. This points to how quickly ADCs are moving into earlier lines of treatment, offering potentially more effective options than traditional chemotherapy for some people with metastatic TNBC.

Learn more in our recent installment of Breast Cancer Breakthroughs: What’s New for Metastatic TNBC?

People with HR+/HER2+ metastatic breast cancer are now eligible to receive palbociclib

Palbociclib is FDA-approved to treat HR+/HER2- metastatic breast cancer. However, about 10-20% of newly diagnosed breast cancers are HER2+. Historically, those with HR+/HER2+ metastatic breast cancer were not eligible to receive palbociclib as part of standard treatment. The phase 3 PATINA trial showed that adding palbociclib to HER2-targeted therapy (trastuzumab and pertuzumab) and hormone therapy improved progression-free survival in patients with HR+/HER2+ metastatic breast cancer. Recently, palbociclib with trastuzumab, with or without pertuzumab, and hormone therapy for HR+/HER2+ metastatic breast cancer has been FDA-approved.

Learn more about the PATINA trial in this clip from our Breast Cancer Breakthroughs series.