Enhertu (fam-trastuzumab deruxtecan-nxki) Letter of Medical Necessity
Enhertu (fam-trastuzumab deruxtecan) has rapidly become one of the most important oncology drugs across multiple tumor types. Prior authorization requires precise HER2 testing documentation — including the distinction between HER2-positive and HER2-low status — and clear prior therapy sequencing.
FDA-Approved Indications
- ● HER2-positive unresectable or metastatic breast cancer (HER2+ and HER2-low)
- ● HER2-positive unresectable or metastatic gastric or GEJ adenocarcinoma
- ● HER2-mutant unresectable or metastatic NSCLC
- ● HER2-positive unresectable or metastatic colorectal cancer
Why Enhertu Prior Authorization Gets Denied
The most common denial reasons across major payers:
- 1. HER2 status not confirmed by validated IHC or ISH assay (HER2 IHC 3+ or ISH-amplified for HER2+; IHC 1+ or IHC 2+/ISH-negative for HER2-low)
- 2. Prior therapy requirements not met (e.g., prior trastuzumab and pertuzumab for HER2+ breast cancer)
- 3. Interstitial lung disease (ILD) risk documentation not addressed
- 4. Line of therapy sequence not established in the record
- 5. ECOG performance status not documented
What to Include in a Enhertu Letter of Medical Necessity
Document HER2 testing with the specific assay used, laboratory, IHC score (3+, 2+, 1+), and ISH result where applicable. For HER2-low breast cancer (IHC 1+ or IHC 2+/ISH-negative), explicitly cite DESTINY-Breast04 and NCCN guidance. Include all prior lines of therapy, ILD risk assessment (history of ILD, baseline chest CT if available), ECOG status, and tumor histology confirmation.
Key clinical evidence to cite:
- ✓ DESTINY-Breast03 — superior PFS and OS vs ado-trastuzumab emtansine in HER2+ metastatic breast cancer
- ✓ DESTINY-Breast04 — PFS and OS benefit in HER2-low breast cancer (novel category)
- ✓ DESTINY-Lung02 — 37.1% ORR in HER2-mutant NSCLC
- ✓ DESTINY-Gastric02 — 38% ORR in HER2+ gastric/GEJ
Relevant guidelines:
- 📖 NCCN Breast Cancer Guidelines (Category 1)
- 📖 NCCN NSCLC Guidelines
- 📖 NCCN Gastric Cancer Guidelines
- 📖 ASCO HER2-Low Breast Cancer Recommendations
Enhertu Prior Authorization Criteria
Standard criteria across major US payers for Enhertu. Specific criteria vary by plan — RxCheckUp tailors each LMN to your patient's exact payer policy.
Typical step therapy requirements:
- → Prior therapy requirements not met (e.g., prior trastuzumab and pertuzumab for HER2+ breast cancer)
Required documentation:
- ✓ ICD-10 diagnosis code with specificity
- ✓ Prior therapy history with dates, doses, and discontinuation reasons
- ✓ Specialist evaluation (where applicable)
- ✓ Baseline disease activity or biomarker results
- ✓ Clinical rationale citing FDA labeling or guidelines
Approval details:
Initial approval: typically 6 months. Renewal: 12 months with documented clinical response.
Payers Covering Enhertu
RxCheckUp tailors each LMN to the specific payer's medical policy and step therapy requirements:
Enhertu Prior Authorization FAQ
Why was my Enhertu prior authorization denied?
The most common denial reasons for Enhertu are: HER2 status not confirmed by validated IHC or ISH assay (HER2 IHC 3+ or ISH-amplified for HER2+; IHC 1+ or IHC 2+/ISH-negative for HER2-low); Prior therapy requirements not met (e.g., prior trastuzumab and pertuzumab for HER2+ breast cancer); Interstitial lung disease (ILD) risk documentation not addressed; Line of therapy sequence not established in the record; ECOG performance status not documented.
What should a Enhertu Letter of Medical Necessity include?
Document HER2 testing with the specific assay used, laboratory, IHC score (3+, 2+, 1+), and ISH result where applicable. For HER2-low breast cancer (IHC 1+ or IHC 2+/ISH-negative), explicitly cite DESTINY-Breast04 and NCCN guidance. Include all prior lines of therapy, ILD risk assessment (history of ILD, baseline chest CT if available), ECOG status, and tumor histology confirmation.
Which payers cover Enhertu?
Enhertu is covered by major US payers including UnitedHealthcare, Aetna, Cigna, BCBS, Medicare Part B, though formulary tier and prior authorization criteria vary.