Top 2025 Treatments for HER2+ and HR+ Breast Cancer in the US

HER2-Positive and HER2-Low Metastatic Breast Cancer

FDA Approval of Enhertu

A noteworthy development includes the FDA approval of fam-trastuzumab deruxtecan-nxki (Enhertu) on January 27, 2025, for treating unresectable or metastatic HR-positive, HER2-low, and HER2-ultralow breast cancer. This approval is especially important for patients who have experienced disease progression following one or more endocrine therapies. Enhertu introduces a new treatment approach, demonstrating statistically significant improvements in progression-free survival (PFS) compared to traditional chemotherapy options, making it a promising alternative for those previously with limited options.

Clinical Evidence from the DESTINY-Breast06 Trial

The effectiveness of Enhertu is strongly backed by the DESTINY-Breast06 Phase III trial, which involved 866 adult patients with HER2-low or HER2-ultralow breast cancer. The trial found that patients treated with Enhertu had a median PFS of 13.2 months as opposed to 8.1 months for those receiving chemotherapy. Notably, the objective response rate (ORR) for Enhertu reached 65.7%, a remarkable improvement over the 30.8% ORR for chemotherapy. Such evidence underscores the efficacy of Enhertu in providing substantial benefits over previous standards of care.

Importance of HER2 Status Testing

This approval highlights the critical importance of accurate HER2 status testing. Utilizing an FDA-approved assay to determine HER2 expression levels permits more personalized treatment plans, enabling more effective therapy decisions tailored to each individual patient’s profile. As treatment options become increasingly targeted, precise diagnostic testing becomes essential in maximizing patient benefit and minimizing unnecessary exposure to less effective therapies.

HR-Positive, HER2-Negative Breast Cancer

Triplet Therapy with Inavolisib

For patients with hormone receptor-positive, HER2-negative breast cancer, particularly those with PIK3CA mutations, a new triplet therapy recently approved by the FDA shows promising results. This innovative therapy combines inavolisib (Itovebi®), fulvestrant (Faslodex®), and palbociclib (Ibrance®). Clinical trials have shown it more than doubles PFS compared to the standard two-drug therapy, offering hope for patients whose cancers have become resistant to earlier treatments.

Phase 3 Trial Results

In a trial involving 325 patients with resistant ER-positive, HER2-negative breast cancers, inavolisib significantly increased the effectiveness of the standard treatment regimen. Participants in the trial had developed resistance to earlier endocrine therapies, with PIK3CA mutations impacting their prognoses. The results suggest this triplet therapy could become a valuable option for this specific breast cancer subtype, potentially improving both response rates and duration of control over the disease.

Impact on Treatment Standards

Shifting Paradigms with Enhertu

The introduction of Enhertu for HER2-low and ultralow breast cancer represents a potential shift in treatment standards. Moving beyond traditional chemotherapy post-endocrine therapy, Enhertu offers an alternative standard for these HER2-expressing subtypes. Its recognition as a breakthrough therapy with priority review indicates its possible impact and contribution to evolving treatment methodologies, marking a new era in targeted breast cancer therapy.

Personalization and Accessibility

Enhertu's approval spotlights the larger movement toward personalized medicine in oncology. Correctly identifying HER2 status and using targeted therapies allows for more individualized treatment plans that match each patient's unique tumor profile. This approach signals significant advancements in patient outcomes and potentially longer survival for breast cancer patients, making personalized care more accessible and effective than ever before.

Conclusion

The year 2025 is a pivotal year in breast cancer treatment with significant advances in therapies for HER2+ and HR+ subtypes. The approval of Enhertu for HER2-low and ultralow breast cancer and the innovative triplet therapy for HR-positive, HER2-negative breast cancer signal new avenues for potentially enhanced patient outcomes. These developments emphasize the importance of personalized medicine and accurate diagnostic testing to provide the most effective treatments available.

Continuing research and development in this field hold promise for further innovations, potentially transforming breast cancer from a chronic disease to a more manageable condition. Both clinicians and patients now have access to treatment options that seemed unattainable just years ago, rendering 2025 a notable year in breast cancer management.

Sources:

• FDA Approval of Enhertu
• AstraZeneca Announcement on Enhertu
• Memorial Sloan Kettering Cancer Center on Inavolisib

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