Datopotamab Deruxtecan-dlnk (Datroway)

Number: 1078

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses datopotamab deruxtecan-dlnk (Datroway) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of datopotamab deruxtecan-dlnk (Datroway) is required of all Aetna participating providers and members in applicable plan designs. For precertification of datopotamab deruxtecan-dlnk (Datroway), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.

Note: Site of Care Utilization Management Policy applies. For information on site of service for datopotamab deruxtecan-dlnk (Datroway), see Utilization Management Policy on Site of Care for Specialty Drug Infusions. 

1. Criteria for Initial Approval
   
   Aetna considers datopotamab deruxtecan-dlnk (Datroway) medically necessary for treatment of the following indications:

   1. Breast Cancer

      1. For treatment of breast cancer, as a single agent, when all of the following criteria are met:
         1. The disease is unresectable or metastatic; and
         2. The cancer cells are hormone receptor positive and HER2-negative; and
         3. The member has received prior treatment including endocrine based therapy and chemotherapy for unresectable or metastatic disease; and
         4. The member is not a candidate for treatment with fam-trastuzumab deruxtecan-nxki (Enhertu).
      2. For the first-line treatment of triple negative breast cancer, as a single agent, when all of the following criteria are met:
         1. The disease is recurrent unresectable or metastatic; and
         2. The cancer cells are estrogen receptor, progesterone receptor, and HER2 (ERBB2) negative; and
         3. The tumor’s PD-L1 CPS is less than 10 and there are no germline BRCA 1/2 pathogenic variants.

   2. Non-Small Cell Lung Cancer (NSCLC)

      Aetna considers datopotamab deruxtecan-dlnk (Datroway) medically necessary for subsequent treatment of EGFR mutation positive recurrent, advanced, or metastatic non-small cell lung cancer when the requested medication is used as a single agent:

      Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers datopotamab deruxtecan-dlnk (Datroway) therapy medically necessary in members requesting reauthorization for an indication listed in the Criteria for Initial Approval section when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Datopotamab deruxtecan-dlnk is supplied as Datroway 100 mg lyophilized powder in a single-dose vial for injection for intravenous infusion only.

• Do not administer as an intravenous push or bolus. Do not use sodium chloride injection, USP.
• Premedicate for prevention of infusion reactions and nausea and vomiting.
• For locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) or unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer:
  

  The recommended dosage of Datroway is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

Source: Daiichi Sankyo, 2025

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
81235	EGFR (epidermal growth factor receptor) (eg, non-small cell lung cancer) gene analysis, common variants (eg, exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q)
88360	Morphometric analysis, tumor immunohistochemistry (eg, Her-2/neu, estrogen receptor/progesterone receptor), quantitative or semiquantitative, per specimen, each single antibody stain procedure; manual
88361	using computer-assisted technology
96413	Chemotherapy administration, IV infusion technique; up to 1 hour, single or initial substance/drug
96415	each additional hour (list in addition to code for primary procedure)
HCPCS codes covered if selection criteria are met:
J9011	Injection, datopotamab deruxtecan-dlnk, 1 mg
Other HCPCS codes related to the CPB:
J9358	Injection, fam-trastuzumab deruxtecan-nxki, 1 mg
ICD-10 codes covered if selection criteria are met:
C34.10 – C34.92	Malignant neoplasm of bronchus and lung
C50.011 – C50.929	Malignant neoplasm of breast
C50.A0 – C50.A2	Malignant inflammatory neoplasm of breast

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Datroway is indicated for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy.
• Datroway is indicated for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received endocrine based therapy and chemotherapy for unresectable or metastatic disease.

Compendial Uses

• Breast Cancer
• Non-Small Cell Lung Cancer (NSCLC)

Datopotamab deruxtecan-dlnk is available as Datroway (Daiichi Sankyo, Inc.), a Trop-2-directed antibody and topoisomerase inhibitor conjugate that is composed of composed of three components: 1) a humanized anti-Trop2 IgG1
monoclonal antibody (mAb), covalently linked to 2) a topoisomerase I inhibitor, via 3) a tetrapeptide-based cleavable linker. Deruxtecan is made up of a protease-cleavable maleimide tetrapeptide linker and the topoisomerase inhibitor, DXd, which is an exatecan derivative. The antibody is manufactured using recombinant DNA technology in Chinese hamster ovary cells, and the topoisomerase inhibitor and linker are manufactured through chemical synthesis. Datroway binds to Trop2 on cells, including tumor cells, and subsequently undergoes internalization and intracellular linker cleavage by lysosomal enzymes. DNA damage and apoptotic cell death results upon release of the membrane-permeable Dxd. Datroway showed anti-tumor activity in a mouse model of breast cancer (Daiichi Sankyo, 2024).

According to the prescribing information, Datroway carries the following warnings and precautions and adverse reactions.

• Warnings and precautions

  • Interstitial lung disease (ILD) and pneumonitis: Datroway can cause severe and fatal cases of ILD/pneumonitis. Monitor for new or worsening signs and symptoms of ILD/pneumonitis. If ILD/pneumonitis is suspected, withhold Datroway and initiate corticosteroids. Permanently discontinue Datroway in patients with confirmed Grade 2 or higher ILD/pneumonitis.
  • Ocular adverse reactions: Datroway can cause ocular adverse reactions including dry eye, keratitis, blepharitis and meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision. Monitor patients for ocular adverse reactions during treatment with Datroway. Dose delay, dose reduce, or permanently discontinue Datroway based on the severity of ocular adverse reactions. Refer patients to an eye care professional for any new or worsening ocular signs and symptoms.
  • Stomatitis/oral mucositis: Datroway can cause stomatitis, including mouth ulcers and oral mucositis. Advise patients to use a steroid-containing mouthwash when starting treatment and to hold ice chips or ice water in mouth during the infusion of Datroway. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue Datroway.
  • Embryo-fetal toxicity: Datroway can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
    
    

• Adverse reactions: The most common adverse reactions (≥20%), including laboratory abnormalities, were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase.

On January 17, 2025, the U.S. Food and Drug Administration (FDA) approved datopotamab deruxtecan-dlnk (Datroway) for the treatment of adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. The FDA approval was based on supporting data from the TROPION-Breast01 study (FDA, 2025a).

In the TROPION-Breast01 study, a global, multicenter, open-label, randomized, phase 3 trial, Bardia et al. (2025) evaluated the efficacy of datopotamab deruxtecan-dlnk (Datroway) in 732 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer. Patients were eligible for this study if they had experienced disease progression, been considered unsuitable for further endocrine therapy, and received one to two lines of prior chemotherapy for unresectable or metastatic disease. Patients were excluded if they had interstitial lung disease (ILD)/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, clinically active brain metastases, or clinically significant corneal disease at screening. Additionally, patients were excluded for an Eastern Cooperative Oncology Group (ECOG) performance status > 1 (Daiichi Sankyo, 2025; FDA, 2025a).

The investigators stratified patient randomization by previous lines of chemotherapy (one or two), prior cyclin-dependent kinase (CDK)4/6 inhibitor (yes or no), and geographical region. Patients were randomized 1:1 to receive either an intravenous infusion of Datroway 6 mg/kg (n=365) every 3 weeks or investigator's choice of chemotherapy (n=367); eribulin (60%), capecitabine (21%), vinorelbine (10%), or gemcitabine (9%) until unacceptable toxicity or disease progression. The dual primary efficacy outcome measures were progression-free survival (PFS), assessed by blinded independent central review (BICR), based on Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) and overall survival (OS). Additional efficacy outcome measures included confirmed objective response rate (ORR) and duration of response (DOR) by BICR (Daiichi Sankyo, 2025; FDA, 2025a). 

The median PFS was 6.9 months (95% Confidence Interval [CI]: 5.7, 7.4) in the Datroway group versus 4.9 months (95% CI: 4.2, 5.5) in the chemotherapy group (Hazard ration 0.63 [95% CI: 0.52, 0.76] two-sided p-value < 0.0001). Median OS was 18.6 months (95% CI: 17.3, 20.1) in the Datroway group versus 18.3 months (95% CI: 17.3, 20.5) in the chemotherapy group (Hazard ratio 1.01 [95% CI: 0.83, 1.22]; two-sided p-value was not statistically significant). Confirmed ORR was 36% (95% CI: 31, 42) and 23% (95% CI: 19, 28) and median DOR was 6.7 months (95% CI: 5.6, 9.8) and 5.7 months (95% CI: 4.9, 6.8) in the Datroway and chemotherapy groups, respectively. The study showed a statistically significant improvement for patients randomized to the Datroway group compared to the chemotherapy group (Daiichi Sankyo, 2025; FDA, 2025a).

On June 23, 2025, the U.S. Food and Drug Administration (FDA) granted accelerated approval to datopotamab deruxetan-dlnk (Datroway) for adults with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy. The FDA approval is based on supporting data from the TROPION-Lung05 and TROPION-Lung01 studies (FDA, 2025b).

Investigators evaluated the efficacy of datopotamab deruxetan-dlnk (Datroway) in a pooled subgroup of patients with locally advanced or metastatic EGFR-mutated NSCLC who were enrolled across the TROPION-Lung05 and TROPION-Lung01 studies. The TROPION-Lung05 study was a global, multicenter, single-arm, open-label trial consisting of patients with previously treated NSCLC with an actionable genomic alteration. The TROPION-Lung01 study was a global, multicenter, randomized, active-controlled, open-label trial consisting of patients with previously treated NSCLC with or without an actionable genomic alteration.

In both trials, eligible patients with EGFR-mutated NSCLC were required to have previously receive an EGFR-directed therapy and platinum-based chemotherapy. Patients were excluded from the studies if they had any of the following: a history of interstitial lung disease (ILD)/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, clinically significant corneal disease at screening, or had brain metastases that were untreated and symptomatic (Daiichi Sankyo, 2025; FDA, 2025b).

Patients received Datroway 6 mg/kg as an intravenous infusion every 3 weeks until unacceptable toxicity or disease progression (Daiichi Sankyo, 2025; FDA, 2025b).

The pooled efficacy population was assessed for the major efficacy outcome measure of overall response rate (ORR) by blinded independent central review (BCIR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Duration of response (DOR) was an additonal efficacy outcome measure. The ORR was 45% (95% Confidence Interval [CI]: 35, 54) and median DOR was 6.5 months (95% CI: 4.2, 8.4) (Daiichi Sankyo, 2025; FDA, 2025b).

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References