Enhertu Shows Promise as First-Line Treatment for HER2-Positive Metastatic Breast Cancer

AstraZeneca and Daiichi Sankyo's antibody-drug conjugate Enhertu (trastuzumab deruxtecan) continues to revolutionize breast cancer treatment, with new data suggesting its potential as a first-line therapy for HER2-positive metastatic breast cancer. Results from the Phase 3 Destiny-Breast09 trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, demonstrate significant improvements in progression-free survival when Enhertu is combined with Perjeta (pertuzumab).

Destiny-Breast09 Trial Results

The Destiny-Breast09 trial compared the combination of Enhertu and Perjeta against the current standard of care for first-line treatment of HER2-positive metastatic breast cancer. The standard regimen, known as THP, consists of Perjeta, Herceptin (trastuzumab), and chemotherapy.

Results showed that patients receiving Enhertu plus Perjeta experienced a median progression-free survival of nearly 41 months, compared to 27 months for those on the THP regimen. This significant 14-month improvement represents a major advancement in the treatment of HER2-positive metastatic breast cancer.

Dr. Vishwanath Sathyanarayanan, a medical oncologist and academic advisor at Apollo Hospitals in Bangalore, India, called the results "a phenomenal advantage in progression-free survival" and "definitely practice-changing."

Additionally, the Enhertu-Perjeta combination achieved a higher rate of complete response, with 15% of patients showing no detectable signs of cancer compared to 8.5% in the THP group.

Safety Considerations and Future Directions

While the efficacy data are impressive, the trial also highlighted important safety considerations. Enhertu's current labeling includes a "black box" warning for interstitial lung disease and pneumonitis, potentially life-threatening side effects. In the Destiny-Breast09 trial, 46 patients in the Enhertu-Perjeta group experienced these side effects, compared to only 4 in the THP group. Two patients in the Enhertu-treated group died as a result.

Dr. Eleonora Teplinsky, head of breast and gynecologic medical oncology at New Jersey's Valley-Mount Sinai Comprehensive Cancer Care, emphasized the need to balance Enhertu's efficacy with its toxicity profile.

The trial's findings raise several questions for future research and clinical practice. These include determining the optimal duration of Enhertu treatment, exploring potential sequencing strategies, and investigating its use in older patient populations, as most trial participants were under 65 years old.

AstraZeneca and Daiichi Sankyo are continuing to evaluate Enhertu's potential in earlier treatment settings, including neo-adjuvant therapy before surgery. The companies recently announced positive results from the Destiny-Breast11 study, which found that Enhertu followed by THP improved complete response rates when used before surgery compared to the standard of care.

As Enhertu's role in breast cancer treatment continues to expand, oncologists and researchers will need to address these outstanding questions to optimize patient outcomes and manage potential risks associated with this powerful new therapy.