Commercial

Medical Policy

Title:

Datopotamab deruxtecan (Datroway®)

Policy #:

08.02.41a

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member's medical needs and condition.

MEDICALLY NECESSARY

Datopotamab deruxtecan-dlnk (Datroway®) is considered medically necessary and, therefore, covered when the following criteria are met, including human epidermal growth factor receptor 2 (HER2) protein overexpression verified by one of the US Food and Drug Administration (FDA)-approved diagnostic tests as listed in the policy guidelines, for any of the following indications:

DATOPOTAMAB DERUXTECAN-DLNK (DATROWAY)

Datopotamab deruxtecan-dlnk (Datroway) is considered medically necessary and, therefore, covered for any of the following indications:

Invasive Breast Cancer

As second or subsequent-line therapy as a single agent for invasive breast cancer for those who have received prior endocrine-based therapy and chemotherapy for recurrent unresectable (local or regional) or stage IV (M1) hormone receptor (HR) positive and HER2 immunohistochemistry (IHC) 0, 1+, or 2+/in situ hybridization (ISH) negative if not a candidate for fam-trastuzumab deruxtecan-nxki OR 2+/ISH negative if not a candidate for fam-trastuzumab deruxtecan-nxki
Single-agent therapy for recurrent unresectable (local or regional) or stage IV (M1) triple-negative breast cancer (TNBC) as first-line therapy if programmed death-ligand 1 (PD-L1) combined positive score (CPS) is less than 10 or not a candidate for PD-1/PD-L1 inhibitor therapy and no germline BRCA 1/2 pathogenic variant (National Comprehensive Cancer Network [NCCN] preferred)

Inflammatory Breast Cancer

As second- or subsequent-line therapy as a single agent for inflammatory breast cancer for those who have received prior endocrine-based therapy and chemotherapy for recurrent unresectable (local or regional) or stage IV (M1), HR positive and HER2 (ERBB2) IHC 0, 1+, or 2+/ISH negative if not a candidate for fam-trastuzumab deruxtecan-nxki
Single-agent therapy for recurrent unresectable (local or regional) or stage IV (M1) TNBC as first-line therapy if PD-L1 CPS is less than 10 or not a candidate for PD-1/PD-L1 inhibitor therapy and no germline BRCA 1/2 pathogenic variant (NCCN preferred)

Unresectable or Metastatic Breast Cancer

For the treatment of individuals with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy.
For the treatment of individuals with unresectable or metastatic, HR-positive, HER2-negative (IHC 0, ICH 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.

Non-small cell lung cancer (NSCLC)

Subsequent systemic therapy as a single agent for recurrent, advanced, or metastatic disease in individuals with performance status 0-2, EGFR mutations including exon 19 del/L858R mutation, S768I, L861Q, G719X or exon 20 insertion, and nonsquamous cell histology (NCCN preferred for subsequent therapy; other recommended option for subsequent progression)

For individuals (≥18 years of age) with locally advanced or metastatic EGFR-mutated NSCLC who have received prior EGFR-directed therapy and platinum-based chemotherapy.

EXPERIMENTAL/INVESTIGATIONAL

All other uses of datopotamab deruxtecan-dlnk (Datroway) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company's medical policy on off-label coverage for prescription drugs and biologics.

MANDATES

PENNSYLVANIA MEMBERS

In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have Stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents" (08.01.08) for additional information regarding the applicable coverage of drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2 (HER2) PROTEIN OVEREXPRESSION TESTING

HER2 protein overexpression is detected either by immunohistochemical (IHC) assay that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample or with a type of in situ hybridization (ISH) test for gene amplification (e.g., fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], dual in situ hybridization [DISH]). The US Food and Drug Administration (FDA) has approved several commercially available tests to aid in the selection of breast cancer individuals for fam-trastuzumab datopotamab deruxtecan-dlnk (Datroway) therapy. The National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) guidelines (2018) further recommend that IHC assay and ISH testing should only be done at laboratories that are accredited to perform HER2 testing.

An IHC test result is reported as 0 or 1+ (negative), 2+ (borderline), or 3+ (positive).
A FISH test result is reported as a HER2 gene/chromosome 17 ratio less than 1.8 (negative), a ratio of 1.8 to less than 2.0 (borderline), or a ratio of 2.0 or greater (positive).
A single-probe ISH test result is reported as average HER2 copy number less than 4.0 signals/cell (negative); 4.0 to less than 6.0 signals/cell (borderline); 6.0 or greater signals/cell (positive).
A dual-probe ISH test result is reported as HER2/CEP17 (chromosome enumeration probe 17) ratio 2.0 or greater (positive); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number less than 4.0 signals/cell (negative); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 4.0 to less than 6.0 signals/cell (borderline); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 6.0 signals/cell or greater (positive).

The NCCN and ASCO both have issued guidelines for HER2 testing in invasive breast cancer that call for confirming a borderline or equivocal result:

IHC assay result of 2+: confirm with ISH test (if same sample), or with a new IHC or ISH test (if new sample available).
FISH assay: confirm with either a repeat FISH test or an additional cell counting and recalculation of the ratio. If a repeat FISH test remains equivocal, then an IHC assay is recommended for confirmation.
Single-probe ISH assay: confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available).
Dual-probe ISH assay: confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).

DRUG INFORMATION

In accordance with FDA prescribing information, datopotamab deruxtecan-dlnk (Datroway) is 6 mg/kg (up to a maximum of 540 mg for individuals ≥90 kg) administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, datopotamab deruxtecan-dlnk (Datroway) is covered under the medical benefits of the Company’s products when the medical necessity criteria and Dosing and Frequency Requirements listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Datopotamab deruxtecan-dlnk (Datroway) was approved by the FDA on January 17, 2025, for the treatment of adult individuals with unresectable or metastatic, hormone receptor (HR)-positive, 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 safety and effectiveness have not been established in pediatric individuals.

Datopotamab deruxtecan-dlnk (Datroway) was approved by the FDA on June 23, 2025, for adult individuals with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

OFF-LABEL INDICATION

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

Description

Datopotamab deruxtecan-dlnk (Datroway) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult individuals 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 prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.

DIAGNOSTIC TESTS FOR HER2 PROTEIN EXPRESSION TESTING

HER2 protein overexpression is detected either by immunohistochemical (IHC) assay that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample or with a type of in situ hybridization (ISH) test for gene amplification (e.g., fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], dual in situ hybridization [DISH]). The US Food and Drug Administration (FDA) has approved several commercially available tests to aid in the selection of individuals with breast cancer for datopotamab deruxtecan-dlnk (Datroway). The National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) guidelines (2018) further recommend that IHC assay and ISH testing should only be done at laboratories that are accredited to perform HER2 testing.

An IHC test result is reported as 0 or 1+ (negative), 2+ (borderline), or 3+ (positive).
A FISH test result is reported as a HER2 gene/chromosome 17 ratio less than 1.8 (negative), a ratio of 1.8 to less than 2.0 (borderline), or a ratio of 2.0 or greater (positive).
A single-probe ISH test result is reported as average HER2 copy number less than 4.0 signals/cell (negative); 4.0 to less than 6.0 signals/cell (borderline); 6.0 or greater signals/cell (positive).
A dual-probe ISH test result is reported as HER2/CEP17 (chromosome enumeration probe 17) ratio 2.0 or greater (positive); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number less than 4.0 signals/cell (negative); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 4.0 to less than 6.0 signals/cell (borderline); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 6.0 signals/cell or greater (positive).

The NCCN and ASCO both have issued guidelines for HER2 testing in invasive breast cancer that call for confirming a borderline or equivocal result:

IHC assay result of 2+: confirm with ISH test (if same sample), or with a new IHC or ISH test (if new sample available).
FISH assay: confirm with either a repeat FISH test or an additional cell counting and recalculation of the ratio. If a repeat FISH test remains equivocal, an IHC assay is recommended for confirmation.
Single-probe ISH assay: confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available).
Dual-probe ISH assay: confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).

PEER-REVIEWED LITERATURE

SUMMARY

The safety of datopotamab deruxtecan-dlnk (Datroway) was evaluated in 360 individuals with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH−) breast cancer who received at least one dose of deruxtecan-dlnk (Datroway) 6 mg/kg in the TROPION-Breast01 trial. Deruxtecan-dlnk (Datroway) was administered by intravenous infusion once every 3 weeks. The median duration of treatment was 6.7 months (range, 0.7–16.1 months) for individuals who received deruxtecan-dlnk (Datroway). Serious adverse reactions occurred in 15% of individuals who received deruxtecan-dlnk (Datroway). Serious adverse reactions in more than 0.5% of individuals who received deruxtecan-dlnk (Datroway) were urinary tract infection (1.9%), COVID-19 infection (1.7%), interstitial lung disease (ILD)/pneumonitis (1.1%), acute kidney injury, pulmonary embolism, vomiting, diarrhea, hemiparesis, and anemia (0.6% each). Fatal adverse reactions occurred in 0.3% of individuals who received deruxtecan-dlnk (Datroway) and were due to ILD/pneumonitis. The study demonstrated a statistically significant improvement in progression-free survival (PFS) in individuals randomly assigned to deruxtecan-dlnk (Datroway) compared to chemotherapy.

The efficacy of datopotamab deruxtecan-dlnk (Datroway) was evaluated in a pooled subgroup of individuals with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who were enrolled across two clinical studies: TROPION-Lung05 and TROPION-Lung01. TROPION-Lung05 (NCT04484142) was a global, multicenter, single-arm, open-label trial in individuals with previously treated NSCLC with an actionable genomic alteration; TROPION-Lung01 (NCT04656652) was a global, multicenter, randomized, active-controlled, open-label trial in individuals with previously treated NSCLC with or without an actionable genomic alteration. For both trials, eligible individuals with EGFR-mutated NSCLC must have previously received an EGFR-directed therapy and platinum-based chemotherapy. Individuals with a history of ILD/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, or clinically significant corneal disease at screening were ineligible. Individuals who had brain metastases that were untreated and symptomatic were also ineligible. Individuals received deruxtecan-dlnk (Datroway) 6 mg/kg by intravenous infusion every 3 weeks until unacceptable toxicity or disease progression.

For the pooled efficacy population, the major efficacy outcome measure was overall response rate (ORR). An additional efficacy outcome was duration of response (DOR). Efficacy was assessed in 114 individuals with EGFR-mutated NSCLC. Fifty-three percent (53%) of individuals had tumors with exon 19 deletions, 34% had exon 21 L858R mutations, 28% had T790M mutations, 2.6% had exon 20 insertion mutations, and 14% had other EGFR mutations. Four percent (4.4%) of individuals received one prior line of systemic therapy, 39% received two prior lines of systemic therapy, and 57% received three or more prior lines of systemic therapy in the locally advanced or metastatic setting. The confirmed ORR was 35.8% (95% CI, 27.8–44.4) overall, and 43.6% (95% CI, 32.4–55.3) and 23.5% (95% CI, 10.7–41.2) in those with EGFR mutations and ALK rearrangements, respectively. The median DOR was 7.0 months (95% CI, 4.2–9.8), and the overall disease control rate was 78.8% (95% CI, 71.0–85.3). The most common treatment-related adverse event was stomatitis (preferred term; any grade: 56.2%; grade ≥3: 9.5%). Five (3.6%) individuals experienced adjudicated treatment-related ILD/pneumonitis, with one (0.7%) grade 5 event.

OFF-LABEL INDICATION

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Hospital Formulary Service (AHFS). Datopotamab deruxtecan-dlnk (Datroway) . Drug Information 2026. [Lexicomp Online Web site]. 08/12/26. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed September 17, 2026.

Centers for Medicare & Medicaid Services (CMS). Guidance for Prior Authorization and Step Therapy for Part B Drugs in Medicare Advantage. 08/07/2018. Available at: https://www.cms.gov/Medicare/Health-Plans/HealthPlansGenInfo/Downloads/MA_Step_Therapy_HPMS_Memo_8_7_2018.pdf. Accessed September 17, 2026.

ClinicalTrials.gov. A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01) Identifier: NCT05104866. First Posted: November 3, 2021; Last Update Posted: August 24, 2026. Available at: https://www.clinicaltrials.gov/study/NCT05104866 . Accessed September 17, 2026.

ClinicalTrials.gov. Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05). ClinicalTrials.gov. Identifier: NCT04484142. First Posted: July 23, 2024; Last Update Posted: March 24, 2026. Available at: https://clinicaltrials.gov/study/NCT04484142?term=NCT04484142&rank=1. Accessed September 17, 2026.

ClinicalTrials.gov. Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer With or Without Actionable Genomic Alterations (TROPION-LUNG01).ClinicalTrials.gov Identifier: NCT04656652 .First Posted: December 7, 2020; Last Update Posted: August 08, 2026. Available at: https://clinicaltrials.gov/study/NCT04656652. Accessed September 17, 2026.

Daiichi Sankyo, Inc., Basking Ridge, NJ. Datopotamab deruxtecan-dlnk (Datroway) labeling.05/2026. Available at:https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Datroway&inline=true. Accessed September 17, 2026.

Eisenhauera EA, Therasseb P, Bogaertsc J, et al. New response evaluation criteria in solid tumors: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. Accessed September 17, 2026.

Elsevier's Clinical Pharmacology Compendium. Datopotamab deruxtecan-dlnk (Datroway). [Clinical Key Web site]. 09/29/2026. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed September 17, 2026.

Lexi-Drugs Compendium. Datopotamab deruxtecan-dlnk. [Lexicomp Online Web site]. 08/10/2026. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed September 17, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Breast Cancer. V6.2026. [NCCN Web site]. 07/29/2026. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf [via free subscription]. Accessed September 17, 2026.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Datopotamab deruxtecan-dlnk, Datroway. Greenwood Village, CO. [Micromedex® Solutions Web site]. 07/09/2026. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed September 17, 2026.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Datopotamab deruxtecan-dlnk (Datroway). [FDA Web site]. Original: 01/17/25. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed September 17, 2026.

US Food and Drug Administration (FDA). Devices @ FDA (HER2). Available at: http://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm. Accessed September 17, 2026.

US Food and Drug Administration (FDA). Datopotamab deruxtecan-dlnk (Datroway) prescribing information & approval letter. [FDA Web site]. 05/2026. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761394s000lbl.pdf. Accessed September 17, 2026.

Wolff AC, Somerfield MR, Dowsett M, et al. Human epidermal growth factor receptor 2 testing in breast cancer. [ASCO.] 02/14/25. Available at: https://www.asco.org/research-guidelines/quality-guidelines/guidelines/breast-cancer#/9751. Accessed September 17, 2026.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

See Attachment A.

HCPCS Level II Code Number(s)

J9011 Injection, datopotamab deruxtecan-dlnk, 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.02.41a:

11/02/2026

This version of the policy will become effective 11/02/2026.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

The following ICD-10 CM codes have been added to this policy:

C33, C34.01, C34.02, C34.11, C34.12, C34.2, C34.31, C34.32, C34.81, C34.82, C34.91, C34.92, C50.011, C50.012 , C50.021, C50.022, C50.111, C50.112, C50.121, C50.122, C50.211, C50.212, C50.221, C50.222, C50.311

Revisions From 08.02.41:

11/03/2025

This version of the policy will become effective 11/03/2025.

This new policy has been issued to communicate the Company’s coverage position and criteria for datopotamab deruxtecan-dlnk (Datroway).

Version Effective Date:

11/2/2026

Version Issued Date: