ANVISA Approves Trastuzumab Deruxtecan: What You Need to Know

Key Takeaways

• Regulatory milestone: ANVISA granted initial approval in January 2022 and expanded the indication in June 2022, based on FDA approval data and the DESTINY-Breast03 trial results.
• Clinical evidence: The phase 3 DESTINY-Breast03 trial (NCT03529110) showed 75.8% of patients alive without progression at 12 months versus 34.1% with trastuzumab emtansine (hazard ratio 0.28; 95% CI, 0.22–0.37; P<0.001).
• Mechanism: Trastuzumab deruxtecan is an antibody-drug conjugate (ADC) delivering a topoisomerase I inhibitor payload to HER2-expressing tumor cells via a cleavable linker.
• Brazilian indication: Approved for HER2-positive unresectable or metastatic breast cancer after one or more prior anti-HER2 regimens, including progression on trastuzumab plus taxane.
• Market impact: The entry creates competitive pressure on existing HER2-targeted therapies and expands second-line treatment options for Brazilian oncologists.

What Is Trastuzumab Deruxtecan?

Trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate (ADC). It combines a humanized anti-HER2 monoclonal antibody with a topoisomerase I inhibitor payload through a cleavable linker. This structure allows selective delivery of cytotoxic chemotherapy to tumor cells that express HER2.

The antibody binds to HER2 receptors on cancer cells. After internalization, enzymes cleave the linker and release the payload. This mechanism distinguishes trastuzumab deruxtecan from earlier HER2-targeted therapies.

When Did ANVISA Approve This Therapy?

ANVISA granted initial marketing authorization for trastuzumab deruxtecan in January 2022. The initial approval covered patients with HER2-positive metastatic or unresectable breast cancer who had received two or more prior anti-HER2 regimens.

In June 2022, ANVISA expanded the indication. The updated label includes patients who received one or more prior anti-HER2 regimens. This expansion followed the strength of clinical data from the DESTINY-Breast03 trial.

What Clinical Evidence Supports the Approval?

The ANVISA approval rests primarily on data from the DESTINY-Breast03 phase 3 trial. Results published in the New England Journal of Medicine in March 2022 provide the key efficacy findings.

The trial enrolled 524 patients with HER2-positive metastatic breast cancer. All participants had prior treatment with trastuzumab and a taxane. Researchers randomized patients to receive either trastuzumab deruxtecan or trastuzumab emtansine.

The primary endpoint was progression-free survival (PFS). At 12 months, 75.8% of patients receiving trastuzumab deruxtecan were alive without disease progression. This compared to 34.1% in the trastuzumab emtansine group. The hazard ratio for progression or death was 0.28 (95% confidence interval [CI], 0.22 to 0.37; P<0.001).

The 12-month overall survival rate was 94.1% with trastuzumab deruxtecan versus 85.9% with trastuzumab emtansine. The hazard ratio for death was 0.55 (95% CI, 0.36 to 0.86).

How Does the Safety Profile Compare?

The safety profile of trastuzumab deruxtecan in DESTINY-Breast03 showed distinct patterns from trastuzumab emtansine. Key adverse events included nausea, fatigue, and vomiting. Interstitial lung disease occurred in a subset of patients and requires monitoring.

Compared to trastuzumab emtansine, trastuzumab deruxtecan showed lower rates of thrombocytopenia and hepatotoxicity. However, the risk of interstitial lung disease represents an important safety consideration for prescribing physicians in Brazil.

What Is the Competitive Position in Brazil?

Trastuzumab deruxtecan enters a Brazilian market with established HER2-targeted therapies. Trastuzumab emtansine previously served as the standard second-line option. The DESTINY-Breast03 head-to-head data provides a clear efficacy differentiation.

The table below compares key clinical parameters:

Parameter	Trastuzumab Deruxtecan	Trastuzumab Emtansine
12-month PFS rate	75.8%	34.1%
12-month OS rate	94.1%	85.9%
Hazard ratio for progression/death	0.28 (95% CI, 0.22–0.37)	Reference
Primary mechanism	Topoisomerase I inhibitor	DM1 microtubule inhibitor

What Are the Access Considerations?

Market access in Brazil depends on several factors beyond regulatory approval. Reimbursement decisions by public and private payers will determine real-world utilization. The competitive pricing relative to existing HER2-targeted therapies will influence formulary placement.

Physician education on the distinct safety profile, particularly interstitial lung disease monitoring, will be essential. Patient selection based on prior anti-HER2 therapy history aligns with the approved indication.

Frequently Asked Questions

Primary Sources

1. FDA Approval Letter: U.S. Food and Drug Administration. Approval Package for BLA 761139: ENHERTU (fam-trastuzumab deruxtecan-nxki). Approved December 20, 2019. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761139Orig1s000Approv.pdf
2. NEJM Publication: Cortes J, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. New England Journal of Medicine. 2022;386(12):1143-1154. https://www.nejm.org/doi/full/10.1056/NEJMoa2115022
3. ClinicalTrials.gov: DESTINY-Breast03 (NCT03529110). DS-8201a Versus T-DM1 for HER2-Positive Unresectable and/or Metastatic Breast Cancer. https://clinicaltrials.gov/study/NCT03529110
4. ANVISA Registration: Agência Nacional de Vigilância Sanitária. Enhertu (trastuzumabe deruxtecana) registration and indication expansion. https://www.gov.br/anvisa/pt-br/assuntos/medicamentos/novos-medicamentos-e-indicacoes/enhertu-trastuzumabe-deruxtecana-1