ANVISA Approves Enhertu: Transforming HER2-Positive Breast Cancer Care in Brazil
Enhertu has received ANVISA approval, marking a significant advancement in the treatment landscape for HER2-positive breast cancer in Brazil.
Quick Answer
Enhertu has received ANVISA approval, marking a significant advancement in the treatment landscape for HER2-positive breast cancer in Brazil.
Key Questions
- What is trastuzumab deruxtecan and how does it work?
- When did ANVISA approve Enhertu for breast cancer in Brazil?
- What were the key results of the DESTINY-Breast03 trial?
- Which patients are eligible for Enhertu treatment in Brazil?
- What safety considerations apply to trastuzumab deruxtecan?
ANVISA approved trastuzumab deruxtecan (Enhertu) in June 2022 for HER2-positive metastatic breast cancer in Brazil, based on data showing a 72% reduction in disease progression risk compared to standard therapy. The antibody-drug conjugate delivers targeted chemotherapy to cancer cells, offering a new treatment option for patients who have received prior anti-HER2 therapy.
Contents9 sections
Key Takeaways
- ANVISA approval: Enhertu received Brazilian marketing authorization on June 27, 2022, for HER2-positive breast cancer after prior anti-HER2 therapy. [ANVISA]
- Clinical efficacy: The DESTINY-Breast03 trial demonstrated a 12-month progression-free survival rate of 75.8% versus 34.1% with trastuzumab emtansine (T-DM1), with a hazard ratio of 0.28 (95% CI, 0.22–0.37; P<0.001). [NEJM]
- Regulatory precedent: The FDA originally approved Enhertu on December 20, 2019, under accelerated approval for HER2-positive metastatic breast cancer after two or more prior anti-HER2 regimens. [FDA]
- Mechanism innovation: Enhertu combines a HER2-targeting monoclonal antibody with a topoisomerase I inhibitor payload via a cleavable tetrapeptide linker, achieving a drug-to-antibody ratio of approximately 8:1. [PubMed]
What Is Trastuzumab Deruxtecan?
Trastuzumab deruxtecan (sold as Enhertu) is an antibody-drug conjugate (ADC) developed by AstraZeneca and Daiichi Sankyo. It combines the HER2-targeting monoclonal antibody trastuzumab with a potent topoisomerase I inhibitor payload called deruxtecan (DXd). The drug is part of a growing class of targeted cancer therapies available in Brazil.
The drug structure uses a cleavable tetrapeptide-based linker (Gly-Gly-Phe-Gly). This enables selective payload release inside tumor cells via tumor-specific enzymes such as cathepsin L. The high drug-to-antibody ratio of approximately 8:1 ensures substantial cytotoxic delivery to cancer cells.
Unlike conventional HER2-targeted therapies that rely on immune-mediated mechanisms, Enhertu delivers chemotherapy directly into cancer cells. The membrane-permeable DXd payload can also diffuse into neighboring cells, creating a "bystander effect" that kills HER2-low or HER2-negative tumor cells adjacent to the target.
What Clinical Evidence Supported the ANVISA Approval?
The ANVISA approval rested primarily on data from the DESTINY-Breast03 Phase III clinical trial. This randomized, open-label study compared trastuzumab deruxtecan against trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane.
The trial enrolled 524 patients. Results published in the New England Journal of Medicine in 2022 showed:
| Endpoint | Trastuzumab Deruxtecan | T-DM1 |
|---|---|---|
| 12-month PFS rate | 75.8% (95% CI, 69.8–80.7) | 34.1% (95% CI, 27.7–40.5) |
| 12-month OS rate | 94.1% (95% CI, 90.3–96.4) | 85.9% (95% CI, 80.9–89.7) |
| Objective response rate | 79.7% (95% CI, 74.3–84.4) | 34.2% (95% CI, 28.5–40.3) |
| Grade ≥3 adverse events | 45.1% | 39.8% |
The hazard ratio for disease progression or death was 0.28 (95% CI, 0.22–0.37; P<0.001), representing a 72% reduction in risk. The hazard ratio for death was 0.55 (95% CI, 0.36–0.86).
Which Patients Qualify for Treatment?
Under the June 2022 ANVISA approval, Enhertu is indicated for adult patients with HER2-positive metastatic or unresectable breast cancer who have previously received an anti-HER2-based treatment regimen. This differs from the original FDA approval, which required two or more prior anti-HER2 regimens.
The approval was later expanded on October 31, 2022, to include patients with HER2-low breast cancer (IHC 1+ or IHC 2+/ISH-) who had received prior systemic therapy. This expansion was based on data from the DESTINY-Breast04 trial.
Brazilian oncologists can now prescribe Enhertu earlier in the treatment sequence than initially approved in other markets. This positions the therapy as a second-line option rather than solely a last-resort treatment.
What Safety Profile Did ANVISA Review?
The safety analysis from DESTINY-Breast03 revealed important considerations for Brazilian prescribers. Any-grade adverse events occurred in 98.1% of trastuzumab deruxtecan patients versus 86.6% with T-DM1.
The most significant safety signal was interstitial lung disease (ILD) or pneumonitis, which occurred in 10.5% of patients receiving trastuzumab deruxtecan compared to 1.9% with T-DM1. Notably, no grade 4 or 5 ILD events were reported in the trial. The FDA has issued a boxed warning for this risk.
Other adverse events of interest included neutropenia and left ventricular dysfunction. The FDA recommends monitoring patients for respiratory symptoms and cardiac function during treatment.
How Does This Approval Impact Brazil's Oncology Market?
The ANVISA approval of Enhertu marks a significant expansion of oncology treatment options in Brazil. Prior to this authorization, Brazilian patients with HER2-positive metastatic breast cancer who progressed on trastuzumab and pertuzumab had limited evidence-based options.
The introduction of ADC technology validates Brazil's regulatory pathway for novel biologics. It demonstrates that ANVISA can efficiently review and approve innovative therapies based on compelling international clinical data.
From a market perspective, the approval creates competition for existing HER2-targeted therapies. The indication expansion to include patients after only one prior anti-HER2 regimen potentially broadens the addressable patient population significantly. This approval strengthens Brazil's position in the Latin American oncology market.
What Developments Are Expected Next?
Ongoing clinical development programs are exploring trastuzumab deruxtecan in combination regimens. The DESTINY-Breast09 trial is evaluating Enhertu plus pertuzumab as first-line therapy for HER2-positive metastatic breast cancer.
Future ANVISA label expansions may follow if global trials demonstrate efficacy in earlier treatment lines or additional tumor types. The success of Enhertu in Brazil could accelerate regulatory pathways for other ADC technologies in the LATAM region.
Pharmacoeconomic analyses will play a critical role in reimbursement decisions by Brazilian public and private payers. Real-world evidence generation within Brazil will support integration into national treatment guidelines.
Frequently Asked Questions
What is trastuzumab deruxtecan and how does it work?
Trastuzumab deruxtecan (Enhertu) is an antibody-drug conjugate (ADC) that combines a HER2-targeting monoclonal antibody with a topoisomerase I inhibitor payload. It delivers cytotoxic chemotherapy directly into HER2-positive cancer cells, with a drug-to-antibody ratio of approximately 8:1. The cleavable linker enables a bystander effect, allowing the payload to kill neighboring tumor cells.
When did ANVISA approve Enhertu for breast cancer in Brazil?
ANVISA approved Enhertu (trastuzumab deruxtecan) on June 27, 2022, for adult patients with HER2-positive metastatic or unresectable breast cancer who had previously received an anti-HER2-based treatment regimen. The approval was based on data from the DESTINY-Breast03 clinical trial.
What were the key results of the DESTINY-Breast03 trial?
The DESTINY-Breast03 trial showed trastuzumab deruxtecan reduced the risk of disease progression or death by 72% compared to trastuzumab emtansine (T-DM1). The 12-month progression-free survival rate was 75.8% versus 34.1% with T-DM1. The objective response rate was 79.7% versus 34.2%.
Which patients are eligible for Enhertu treatment in Brazil?
Under the ANVISA approval, Enhertu is indicated for adult patients with HER2-positive metastatic or unresectable breast cancer who have previously received an anti-HER2-based treatment regimen. In October 2022, ANVISA expanded the indication to include HER2-low breast cancer patients.
What safety considerations apply to trastuzumab deruxtecan?
Interstitial lung disease (ILD) or pneumonitis occurred in 10.5% of patients receiving trastuzumab deruxtecan in DESTINY-Breast03, compared to 1.9% with T-DM1. No grade 4 or 5 ILD events were reported. Grade 3 or higher adverse events occurred in 45.1% of T-DXd patients versus 39.8% with T-DM1. FDA requires a boxed warning for ILD and pneumonitis.
Primary Sources
- National Health Surveillance Agency of Brazil (ANVISA). Enhertu (trastuzumabe deruxtecana): nova indicação. June 27, 2022. Available at: gov.br/anvisa
- Cortes J, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. New England Journal of Medicine. 2022;386(12):1143-1154. DOI: 10.1056/NEJMoa2115022
- U.S. Food and Drug Administration. Approval Package: Enhertu (fam-trastuzumab deruxtecan-nxki). December 20, 2019. Available at: accessdata.fda.gov
- European Medicines Agency. Enhertu EPAR Summary. Conditional marketing authorization granted January 18, 2021. Available at: ema.europa.eu
- ClinicalTrials.gov. DESTINY-Breast03 (NCT03529110). Phase III trial comparing trastuzumab deruxtecan vs trastuzumab emtansine. Available at: clinicaltrials.gov
- National Health Surveillance Agency of Brazil (ANVISA). Enhertu (trastuzumabe deruxtecana): nova indicação HER2-low. October 31, 2022. Available at: gov.br/anvisa
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