Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.
Effective February 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Fam-trastuzumab deruxtecan-nxki (e.g., Enhertu) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness improving health outcomes when ALL the following criteria are met:
For labeled indications, all products must be dosed in accordance with the label unless otherwise specified.
For off-label indications, authorizations will not exceed 6.4 milligrams per kilogram of body weight every 3 weeks OR maximum recommended doses as outlined in dosage and administration section unless medical literature supports a higher dose.
HER-2 POSITIVE BREAST CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual has a diagnosis of unresectable or metastatic HER2-positive breast cancer and has received prior anti-HER2 based regimens either in the metastatic setting or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy (Enhertu, 2024); AND
2. Individual is 18 years or age or older (Enhertu, 2024); AND
3. Individual has documentation of unresectable and/or metastatic HER2 breast cancer:
a. Circumferential membrane staining that is complete, intense and in greater than 10% of tumor cells (IHC 3+) – diagnosis is HER2 positive (Wolff, 2018); OR
b. If the HER2/CEP17 ratio remains less than 2.0 with greater than or equal to 6.0 HER2 signals per cell, diagnosis is HER2 positive (Wolff, 2018); OR
4. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent as second-line therapy (preferred) (NCCN 1); AND
5. Individual has an ECOG score of 0-1; AND
6. Individual does NOT have any of the following:
a. Pneumonitis or interstitial lung disease (NCCN, 2021); OR
b. Symptomatic congestive heart failure.
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
INVASIVE BREAST CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual has a diagnosis of invasive breast cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used in second-line (NCCN 1) or later line therapy (NCCN 2A) as a single-agent for recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2) IHC 1+ or 2+ and ISH negative disease that is:
a. Hormone receptor negative; OR
b. Hormone receptor positive with visceral crisis or endocrine therapy refractory; OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent for recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2)-positive disease that is hormone receptor-negative, or hormone receptor-positive with or without endocrine therapy as a:
a. Second-line therapy (NCCN 1); OR
b. First-line therapy for select individuals (i.e., those with rapid progression within 6 months of neoadjuvant or adjuvant therapy (12 months for pertuzumab-containing regimens, NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
INFLAMMATORY BREAST CANCER
1. Individual has a diagnosis of inflammatory breast cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used second-line (NCCN 1) or later line therapy (NCCN 2A) as a single-agent for recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2) IHC 1+ or 2+ and ISH negative disease that is:
a. Hormone receptor negative; OR
b. Hormone receptor positive with visceral crisis or endocrine therapy refractory; OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent for recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2)-positive disease that is hormone receptor-negative, or hormone receptor-positive with or without endocrine therapy as a:
a. Second-line therapy (NCCN 1); OR
b. First-line therapy for select individuals (i.e., those with rapid progression within 6 months of neoadjuvant or adjuvant therapy (12 months for pertuzumab-containing regimens, NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
HER-2 POSITIVE BREAST CANCER WITH BRAIN METASTASES
1. Individual has a diagnosis of HER-2 positive breast cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent treatment for limited brain metastases in HER2 positive breast cancer as:
a. Initial treatment in select cases (e.g., small asymptomatic brain metastases) (NCCN 2A); OR
b. Treatment for recurrent brain metastases (NCCN 2A); OR
c. Treatment of relapsed disease with either stable systemic disease reasonable systemic treatment options (NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent treatment for extensive brain metastases in HER2 positive breast cancer as:
a. Primary treatment in select cases (e.g., small asymptomatic brain metastases) (NCCN 2A); OR
b. Treatment for recurrent disease with stable systemic disease or reasonable systemic treatment options(NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
COLON CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual has a diagnosis of colon adenocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as adjuvant treatment for unresectable metachronous metastases (HER2-amplified, IHC3+) that converted to resectable disease after initial treatment. Biologic therapy is only appropriate for continuation of favorable response from conversion therapy (pMMR/MSS or ineligible for or progressed on checkpoint inhibitor immunotherapy for dMMR/MSI-H or polymerase epsilon/delta [POLE/POLD1] mutation, NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as initial treatment as a single agent in patients (HER2-amplified, IHC 3+)(proficient mismatch repair/microsatellite-stable [pMMR/MSS]) for patients with unresectable metachronous metastases and previous FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months (NCCN 2A); OR
4. Fam-trastuzumab deruxtecan-nxki will be used as a second-line and subsequent therapy (biomarker-directed) as a single agent, if not previously given, for progression of advanced or metastatic disease (proficient mismatch repair/microsatellite-stable [pMMR/MSS] or ineligible for or progressed on checkpoint inhibitor immunotherapy for deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] or polymerase epsilon/delta [POLE/POLD1] mutation)(HER2-amplified, IHC 3+) (NCCN 2A); OR
5. Individual has a diagnosis of appendiceal adenocarcinoma and fam-trastuzumab deruxtecan-nxki will be used as a second-line and subsequent therapy (biomarker-driven) as a single agent, if not previously given, for progression of advanced or metastatic disease (proficient mismatch repair/microsatellite-stable (pMMR/MSS) or ineligible for or progressed on checkpoint inhibitor immunotherapy for deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] or polymerase epsilon/delta [POLE/POLD1] mutation)(HER2-amplified, IHC 3+) (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
RECTAL CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual has a diagnosis of rectal adenocarcinoma (HER2-amplified, IHC 3+); AND
2. Fam-trastuzumab deruxtecan-nxki will be used in initial treatment as a single agent for individuals with unresectable metachronous metastases (proficient mismatch repair/microsatellite-stable [pMMR/MSS]) and previous FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months (NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a second-line and subsequent therapy as a single agent, if not previously given, for progression of advanced or metastatic disease (HER2-amplified, IHC 3+) (proficient mismatch repair/microsatellite-stable [pMMR/MSS] or ineligible for or progressed on checkpoint inhibitor immunotherapy for deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] or polymerase epsilon/delta [POLE/POLD1] mutation) NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
ESOPHAGEAL OR ESOPHAGOGASTRIC JUNCTION CANCERS
1. Individual has a diagnosis of esophageal or esophagogastric junction cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a palliative therapy for patients with HER2 overexpression positive adenocarcinoma who are not surgical candidates or have unresectable locally advanced, recurrent, or metastatic disease and Karnofsky performance score ≥60% or ECOG performance score ≤2 as preferred second-line or subsequent therapy as a single agent (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
GALLBLADDER CANCER
1. Individual has a diagnosis of gallbladder adenocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used in subsequent treatment as a single agent for progression on or after systemic treatment for unresectable or resected gross residual (R2) disease or metastatic disease that is HER2-positive (IHC3+) (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
CHOLANGIOCARCINOMA
1. Individual has a diagnosis of intrahepatic cholangiocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used in subsequent treatment as a single agent for progression on or after systemic treatment for unresectable or resected gross residual (R2) disease or metastatic disease that is HER2-positive (IHC3+) (NCCN 2A); OR
3. Individual has a diagnosis of extrahepatic cholangiocarcinoma and Fam-trastuzumab deruxtecan-nxki will be used in a Subsequent treatment as a single agent for progression on or after systemic treatment for unresectable or resected gross residual (R2) disease or metastatic disease that is HER2-positive (IHC3+) (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
NON-SMALL CELL LUNG CANCER
1. Individual has a diagnosis of non-small cell lung cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used in subsequent therapy as a single agent for ERBB2 (HER2) mutation positive recurrent, advanced, or metastatic disease (NCCN 2A) with exception of locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease; OR
3. Fam-trastuzumab deruxtecan-nxki will be used in subsequent systemic therapy as a single agent recurrent, advanced, or metastatic disease in those with performance status 0-2 whose tumors have HER2 overexpression (IHC 3+) (NCCN 2A) with exception of locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease.
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
BLADDER CANCER
1. Individual has a diagnosis of urothelial carcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as second-line systemic therapy (if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor), or as subsequent-line systemic therapy (individuals should have already received platinum and a checkpoint inhibitor, if eligible) as a single agent orHER2 positive, IHC 3+ for:
a. Stage II (cT2, N0) disease or stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present following reassessment of tumor status 2-3 months after primary treatment with concurrent bladder preserving chemoradiotherapy and maximal TURBT (NCCN 2A); OR
b. Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy or concurrent chemoradiotherapy (NCCN 2A); OR
c. Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with first-line systemic therapy or concurrent chemoradiotherapy (NCCN 2A); OR
d. Stage IVA (any T, any N, M1a) disease if stable disease or progression following reassessment of tumor status after primary treatment with first-line systemic therapy (NCCN 2A); OR
e. Metastatic stage IVB (any T, any N, M1b) disease (NCCN 2A); OR
f. Muscle invasive local recurrence or persistent disease in a preserved bladder treated with curative intent (NCCN 2A); OR
g. Metastatic or local recurrence post cystectomy treated with curative intent (NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as therapy for metastatic disease as a single agent for HER2-positive, IHC 3+ disease as a:
a. Second-line systemic therapy if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor (NCCN 2A); OR
b. Subsequent-line systemic therapy (individuals should have already received platinum and a checkpoint inhibitor, if eligible) (NCCN 2A); OR
4. Fam-trastuzumab deruxtecan-nxki will be used in urothelial carcinoma of the prostate in a therapy for metastatic disease as a single agent for HER2-positive, IHC 3+ as:
a. Second-line systemic therapy if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor (NCCN 2A); OR
b. Subsequent-line systemic therapy (individuals should have already received platinum and a checkpoint inhibitor, if eligible) (NCCN 2A); OR
5. Fam-trastuzumab deruxtecan-nxki will be used in primary carcinoma of the urethra as a therapy for recurrent or metastatic disease as a single agent for HER2-positive, IHC3+ as:
a. Second-line systemic therapy if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor (NCCN 2A); OR
b. Subsequent-line systemic therapy (individuals should have already received platinum and a checkpoint inhibitor, if eligible) (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
PANCREATIC CANCER
1. Individual has a diagnosis of pancreatic cancer with HER2 positive (IHC3+) status; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a subsequent therapy as a single agent for locally advanced or metastatic disease and disease progression if good performance status (defined as ECOG PS 0-1, with good biliary drainage and adequate nutritional intake) (NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a single agent alternative systemic therapy if not previously used if good performance status (ECOG PS 0-1) for:
a. Local recurrence in the pancreatic operative bed after resection (NCCN 2A); OR
b. Recurrent metastatic disease with or without local recurrence after resection (NCCN 2A).
GASTRIC CANCER
1. Individual has a diagnosis of gastric adenocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a palliative therapy for HER2 overexpression positive individuals who are not surgical candidates or have unresectable locally advanced, recurrent, or metastatic disease (including peritoneal only metastatic disease, including positive cytology) and Karnofsky performance score ≥60% or ECOG performance score ≤2 as preferred second-line or subsequent therapy as a single agent (NCCN 2A).
VULVAR CANCER
1. Individual has a diagnosis of vulvar cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy for advanced or recurrent/metastatic disease as a single agent for HER-2 positive (IHC 3+ or 2+) tumors (NCCN 2A).
CERVICAL CANCER
1. Individual has a diagnosis of cervical cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy as a single agent for HER-2 positive (IHC 3+ or 2+) tumors with:
a. Local or regional recurrence (NCCN 2A); OR
b. Stage IVB or recurrence with distant metastases (NCCN 2A).
VAGINAL CANCER
1. Individual has a diagnosis of vaginal cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy as a single agent for HER-2 positive (IHC 3+ or 2+) tumors with:
a. Local or regional recurrence (NCCN 2A); OR
b. Stage IVB or recurrence with distant metastases (NCCN 2A).
ENDOMETRIAL CANCER
1. Individual has a diagnosis of endometrial cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy as a single agent for recurrent disease that is HER-2 positive (IHC 3+ or 2+) tumor:
a. May be considered for isolated metastases (NCCN 2A); OR
b. For disseminated metastases with or without sequential palliative external beam radiation therapy (EBRT) (NCCN 2A); OR
c. With sequential EBRT and with or without brachytherapy for locoregional recurrence in patients with no prior RT to site of recurrence, or previous vaginal brachytherapy only (NCCN 2A); OR
d. After surgical exploration, with sequential EBRT for locoregional recurrence inpatients with disease confined to the vagina or paravaginal soft tissue, or in pelvic or para-aortic lymph nodes (NCCN 2A); OR
e. After surgical exploration, with or without sequential EBRT for locoregional recurrence in patients with upper abdominal or peritoneal disease (NCCN 2A); OR
f. With or without sequential palliative EBRT or brachytherapy for locoregional recurrence in patients who have received prior EBRT to site of recurrence (NCCN 2A).
SMALL BOWEL ADENOCARCINOMA
1. Individual has a diagnosis of small bowel adenocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy as a single agent for advanced or metastatic disease that is HER2-amplified (IHC 3+) (if not previously given) (NCCN 2A).
SALIVARY GLAND TUMOR
1. Individual has a diagnosis of salivary gland tumor; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent systemic therapy for human epidermal growth factor receptor 2 (HER2)-positive recurrent disease with:
a. Distant metastases in patients with a performance status (PS) of 0-3 (NCCN 2A); OR
b. Unresectable locoregional recurrence or second primary with prior radiation therapy (NCCN 2A).
OVARIAN, FALLOPIAN TUBE AND PRIMARY PERITONEAL CANCER
1. Individual has a diagnosis of ovarian cancer or fallopian tube cancer or primary peritoneal cancer of endometroid (including grade 1 endometroid carcinoma), serous (including low-grade serous carcinoma), clear cell, mucinous carcinoma or carcinosarcoma histology; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent therapy for platinum-resistant persistent disease or recurrence in HER2- positive tumors [IHC 3+ or 2+] for:
a. Progression on primary, maintenance, or recurrence therapy (NCCN 2A); OR
b. Stable or persistent disease (if not on maintenance therapy) (NCCN 2A); OR
c. Complete remission and relapse <6 months after completing chemotherapy (NCCN 2A).
OCCULT PRIMARY DISEASE
1. Individual has a diagnosis of adenocarcinoma or carcinoma with HER2-positive [IHC 3+] tumors (not otherwise specified) occult primary disease; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a single agent in symptomatic individuals with performance status (PS) 1-2 or asymptomatic patients with PS 0 and aggressive disease that is metastatic or where surgical resection is likely to result in severe morbidity, and that has progressed on or following prior systemic treatment and has no satisfactory alternative treatment options for:
a. Axillary involvement in those with a prostate or post-prostatectomy if clinically indicated (NCCN 2A); OR
b. Lung nodules or breast marker-negative pleural effusion(NCCN 2A); OR
c. Resectable liver disease (NCCN 2A); OR
d. Peritoneal mass or ascites with non-ovarian histology (NCCN 2A); OR
e. Retroperitoneal mass of non-germ cell histology in selected individuals (NCCN 2A); OR
f. Unresectable liver disease or disseminated metastases(NCCN 2A); OR
3. Individual has a diagnosis of squamous cell carcinoma with HER2-positive [IHC 3+] tumors occult primary disease and fam-trastuzumab deruxtecan-nxki will be used as a single agent in symptomatic individuals with performance status (PS) 1-2 or asymptomatic individuals with PS 0 and aggressive disease for systemic therapy in individuals with multiple lung nodules, pleural effusion, or disseminated metastases that progressed on or following prior systemic treatment and have no satisfactory alternative treatment options (NCCN 2A).
Policy Guidelines
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
- 0 = Fully active, able to carry on all pre-disease performance without restriction
- 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework, office work
- 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
- 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
- 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
- 5 = Dead
The use of this drug is covered if a -approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosage and Administration
Dosing per Guidelines where applicable. For off-label indications, authorizations will not exceed 6.4 milligrams per kilogram of body weight every 3 weeks OR maximum recommended doses as outlined below unless medical literature supports a higher dose.
Breast Cancer – HER2 and HER2 low
The recommended dose is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21 day-cycle) until disease progression or unacceptable toxicity.
Gastric Cancer
The recommended dose 6.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cle) until disease progression or unacceptable toxicity.
NSCLC
The recommended dosage for lung cancer is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
Please see prescription guidance for recommended dose modifications, temporary interruption or treatment discontinuation in management of adverse reactions.
HER2-positive solid tumors
The recommended dose is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21 day-cycle) until disease progression or unacceptable toxicity.
Fam-trastuzumab deruxtecan-nxki (e.g., Enhertu) is available as 100 mg lyophilized powder in a single-dose vial.
Fam-trastuzumab deruxtecan-nxki (e.g., Enhertu) should be administered as an intravenous infusion by a healthcare professional.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Fam-trastuzumab deruxtecan-nxki (e.g., Enhertu), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, fam-trastuzumab deruxtecan-nxki (e.g., Enhertu), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificate of coverage.
Effective January 1, 2025 January 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Fam-trastuzumab deruxtecan-nxki (e.g., Enhertu) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness improving health outcomes when ALL the following criteria are met:
For labeled indications, all products must be dosed in accordance with the label unless otherwise specified.
For off-label indications, authorizations will not exceed 6.4 milligrams per kilogram of body weight every 3 weeks OR maximum recommended doses as outlined in dosage and administration section unless medical literature supports a higher dose.
HER-2 POSITIVE BREAST CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual has a diagnosis of unresectable or metastatic HER2-positive breast cancer and has received prior anti-HER2 based regimens either in the metastatic setting or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy (Enhertu, 2024); AND
2. Individual is 18 years or age or older (Enhertu, 2024); AND
3. Individual has documentation of unresectable and/or metastatic HER2 breast cancer:
a. Circumferential membrane staining that is complete, intense and in greater than 10% of tumor cells (IHC 3+) – diagnosis is HER2 positive (Wolff, 2018); OR
b. If the HER2/CEP17 ratio remains less than 2.0 with greater than or equal to 6.0 HER2 signals per cell, diagnosis is HER2 positive (Wolff, 2018); OR
4. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent as second-line therapy (preferred) (NCCN 1); AND
5. Individual has an ECOG score of 0-1; AND
6. Individual does NOT have any of the following:
a. Pneumonitis or interstitial lung disease (NCCN, 2021); OR
b. Symptomatic congestive heart failure.
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
COLON CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual has a diagnosis of colon adenocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as adjuvant treatment for unresectable metachronous metastases (HER2-amplified, IHC3+) that converted to resectable disease after initial treatment. Biologic therapy is only appropriate for continuation of favorable response from conversion therapy (pMMR/MSS or ineligible for or progressed on checkpoint inhibitor immunotherapy for dMMR/MSI-H or polymerase epsilon/delta [POLE/POLD1] mutation, NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as initial treatment as a single agent in patients (HER2-amplified, IHC 3+)(proficient mismatch repair/microsatellite-stable [pMMR/MSS]) for patients with unresectable metachronous metastases and previous FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months (NCCN 2A); OR
4. Fam-trastuzumab deruxtecan-nxki will be used as a second-line and subsequent therapy (biomarker-directed) as a single agent, if not previously given, for progression of advanced or metastatic disease (proficient mismatch repair/microsatellite-stable [pMMR/MSS] or ineligible for or progressed on checkpoint inhibitor immunotherapy for deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] or polymerase epsilon/delta [POLE/POLD1] mutation)(HER2-amplified, IHC 3+) (NCCN 2A); OR
5. Individual has a diagnosis of appendiceal adenocarcinoma and fam-trastuzumab deruxtecan-nxki will be used as a second-line and subsequent therapy (biomarker-driven) as a single agent, if not previously given, for progression of advanced or metastatic disease (proficient mismatch repair/microsatellite-stable (pMMR/MSS) or ineligible for or progressed on checkpoint inhibitor immunotherapy for deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] or polymerase epsilon/delta [POLE/POLD1] mutation)(HER2-amplified, IHC 3+) (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
RECTAL CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual has a diagnosis of rectal adenocarcinoma (HER2-amplified, IHC 3+); AND
2. Fam-trastuzumab deruxtecan-nxki will be used in initial treatment as a single agent for individuals with unresectable metachronous metastases (proficient mismatch repair/microsatellite-stable [pMMR/MSS]) and previous FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months (NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a second-line and subsequent therapy as a single agent, if not previously given, for progression of advanced or metastatic disease (HER2-amplified, IHC 3+) (proficient mismatch repair/microsatellite-stable [pMMR/MSS] or ineligible for or progressed on checkpoint inhibitor immunotherapy for deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] or polymerase epsilon/delta [POLE/POLD1] mutation) NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
INVASIVE BREAST CANCER
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual has a diagnosis of invasive breast cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used in second-line (NCCN 1) or later line therapy (NCCN 2A) as a single-agent for recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2) IHC 1+ or 2+ and ISH negative disease that is:
a. Hormone receptor negative; OR
b. Hormone receptor positive with visceral crisis or endocrine therapy refractory; OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent for recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2)-positive disease that is hormone receptor-negative, or hormone receptor-positive with or without endocrine therapy as a:
a. Second-line therapy (NCCN 1); OR
b. First-line therapy for select individuals (i.e., those with rapid progression within 6 months of neoadjuvant or adjuvant therapy (12 months for pertuzumab-containing regimens, NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
INFLAMMATORY BREAST CANCER
1. Individual has a diagnosis of inflammatory breast cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used second-line (NCCN 1) or later line therapy (NCCN 2A) as a single-agent for recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2) IHC 1+ or 2+ and ISH negative disease that is:
a. Hormone receptor negative; OR
b. Hormone receptor positive with visceral crisis or endocrine therapy refractory; OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent for recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2)-positive disease that is hormone receptor-negative, or hormone receptor-positive with or without endocrine therapy as a:
a. Second-line therapy (NCCN 1); OR
b. First-line therapy for select individuals (i.e., those with rapid progression within 6 months of neoadjuvant or adjuvant therapy (12 months for pertuzumab-containing regimens, NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
HER-2 POSITIVE BREAST CANCER WITH BRAIN METASTASES
1. Individual has a diagnosis of HER-2 positive breast cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent treatment for limited brain metastases in HER2 positive breast cancer as:
a. Initial treatment in select cases (e.g., small asymptomatic brain metastases) (NCCN 2A); OR
b. Treatment for recurrent brain metastases (NCCN 2A); OR
c. Treatment of relapsed disease with either stable systemic disease reasonable systemic treatment options (NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent treatment for extensive brain metastases in HER2 positive breast cancer as:
a. Primary treatment in select cases (e.g., small asymptomatic brain metastases) (NCCN 2A); OR
b. Treatment for recurrent disease with stable systemic disease or reasonable systemic treatment options(NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
ESOPHAGEAL OR ESOPHAGOGASTRIC JUNCTION CANCERS
1. Individual has a diagnosis of esophageal or esophagogastric junction cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a palliative therapy for patients with HER2 overexpression positive adenocarcinoma who are not surgical candidates or have unresectable locally advanced, recurrent, or metastatic disease and Karnofsky performance score ≥60% or ECOG performance score ≤2 as preferred second-line or subsequent therapy as a single agent (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
GALLBLADDER CANCER
1. Individual has a diagnosis of gallbladder adenocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used in subsequent treatment as a single agent for progression on or after systemic treatment for unresectable or resected gross residual (R2) disease or metastatic disease that is HER2-positive (IHC3+) (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
CHOLANGIOCARCINOMA
1. Individual has a diagnosis of intrahepatic cholangiocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used in subsequent treatment as a single agent for progression on or after systemic treatment for unresectable or resected gross residual (R2) disease or metastatic disease that is HER2-positive (IHC3+) (NCCN 2A); OR
3. Individual has a diagnosis of extrahepatic cholangiocarcinoma and Fam-trastuzumab deruxtecan-nxki will be used in a Subsequent treatment as a single agent for progression on or after systemic treatment for unresectable or resected gross residual (R2) disease or metastatic disease that is HER2-positive (IHC3+) (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
NON SMALL CELL LUNG CANCER
1. Individual has a diagnosis of non-small cell lung cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used in subsequent therapy as a single agent for ERBB2 (HER2) mutation positive recurrent, advanced, or metastatic disease (NCCN 2A) with exception of locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease; OR
3. Fam-trastuzumab deruxtecan-nxki will be used in subsequent systemic therapy as a single agent recurrent, advanced, or metastatic disease in those with performance status 0-2 whose tumors have HER2 overexpression (IHC 3+) (NCCN 2A) with exception of locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease.
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
BLADDER CANCER
1. Individual has a diagnosis of urothelial carcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as second-line systemic therapy (if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor), or as subsequent-line systemic therapy (individuals should have already received platinum and a checkpoint inhibitor, if eligible) as a single agent orHER2 positive, IHC 3+ for:
a. Stage II (cT2, N0) disease or stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present following reassessment of tumor status 2-3 months after primary treatment with concurrent bladder preserving chemoradiotherapy and maximal TURBT (NCCN 2A); OR
b. Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy or concurrent chemoradiotherapy (NCCN 2A); OR
c. Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with first-line systemic therapy or concurrent chemoradiotherapy (NCCN 2A); OR
d. Stage IVA (any T, any N, M1a) disease if stable disease or progression following reassessment of tumor status after primary treatment with first-line systemic therapy (NCCN 2A); OR
e. Metastatic stage IVB (any T, any N, M1b) disease (NCCN 2A); OR
f. Muscle invasive local recurrence or persistent disease in a preserved bladder treated with curative intent (NCCN 2A); OR
g. Metastatic or local recurrence post cystectomy treated with curative intent (NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as therapy for metastatic disease as a single agent for HER2-positive, IHC 3+ disease as a:
a. Second-line systemic therapy if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor (NCCN 2A); OR
b. Subsequent-line systemic therapy (individuals should have already received platinum and a checkpoint inhibitor, if eligible) (NCCN 2A); OR
4. Fam-trastuzumab deruxtecan-nxki will be used in urothelial carcinoma of the prostate in a therapy for metastatic disease as a single agent for HER2-positive, IHC 3+ as:
a. Second-line systemic therapy if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor (NCCN 2A); OR
b. Subsequent-line systemic therapy (individuals should have already received platinum and a checkpoint inhibitor, if eligible) (NCCN 2A); OR
5. Fam-trastuzumab deruxtecan-nxki will be used in primary carcinoma of the urethra as a therapy for recurrent or metastatic disease as a single agent for HER2-positive, IHC3+ as:
a. Second-line systemic therapy if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor (NCCN 2A); OR
b. Subsequent-line systemic therapy (individuals should have already received platinum and a checkpoint inhibitor, if eligible) (NCCN 2A).
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit form continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
3. Individual does not have unacceptable toxicity resulting from the treatment (e.g., severe infusion-related reactions, severe immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions).
PANCREATIC CANCER
1. Individual has a diagnosis of pancreatic cancer with HER2 positive (IHC3+) status; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a subsequent therapy as a single agent for locally advanced or metastatic disease and disease progression if good performance status (defined as ECOG PS 0-1, with good biliary drainage and adequate nutritional intake) (NCCN 2A); OR
3. Fam-trastuzumab deruxtecan-nxki will be used as a single agent alternative systemic therapy if not previously used if good performance status (ECOG PS 0-1) for:
a. Local recurrence in the pancreatic operative bed after resection (NCCN 2A); OR
b. Recurrent metastatic disease with or without local recurrence after resection (NCCN 2A).
GASTRIC CANCER
1. Individual has a diagnosis of gastric adenocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a palliative therapy for HER2 overexpression positive individuals who are not surgical candidates or have unresectable locally advanced, recurrent, or metastatic disease (including peritoneal only metastatic disease, including positive cytology) and Karnofsky performance score ≥60% or ECOG performance score ≤2 as preferred second-line or subsequent therapy as a single agent (NCCN 2A).
VULVAR CANCER
1. Individual has a diagnosis of vulvar cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy for advanced or recurrent/metastatic disease as a single agent for HER-2 positive (IHC 3+ or 2+) tumors (NCCN 2A).
CERVICAL CANCER
1. Individual has a diagnosis of cervical cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy as a single agent for HER-2 positive (IHC 3+ or 2+) tumors with:
a. Local or regional recurrence (NCCN 2A); OR
b. Stage IVB or recurrence with distant metastases (NCCN 2A).
VAGINAL CANCER
1. Individual has a diagnosis of vaginal cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy as a single agent for HER-2 positive (IHC 3+ or 2+) tumors with:
a. Local or regional recurrence (NCCN 2A); OR
b. Stage IVB or recurrence with distant metastases (NCCN 2A).
ENDOMETRIAL CANCER
1. Individual has a diagnosis of endometrial cancer; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy as a single agent for recurrent disease that is HER-2 positive (IHC 3+ or 2+) tumor:
a. May be considered for isolated metastases (NCCN 2A); OR
b. For disseminated metastases with or without sequential palliative external beam radiation therapy (EBRT) (NCCN 2A); OR
c. With sequential EBRT and with or without brachytherapy for locoregional recurrence in patients with no prior RT to site of recurrence, or previous vaginal brachytherapy only (NCCN 2A); OR
d. After surgical exploration, with sequential EBRT for locoregional recurrence inpatients with disease confined to the vagina or paravaginal soft tissue, or in pelvic or para-aortic lymph nodes (NCCN 2A); OR
e. After surgical exploration, with or without sequential EBRT for locoregional recurrence in patients with upper abdominal or peritoneal disease (NCCN 2A); OR
f. With or without sequential palliative EBRT or brachytherapy for locoregional recurrence in patients who have received prior EBRT to site of recurrence (NCCN 2A).
SMALL BOWEL ADENOCARCINOMA
1. Individual has a diagnosis of small bowel adenocarcinoma; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a second-line or subsequent therapy as a single agent for advanced or metastatic disease that is HER2-amplified (IHC 3+) (if not previously given) (NCCN 2A).
SALIVARY GLAND TUMOR
1. Individual has a diagnosis of salivary gland tumor; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent systemic therapy for human epidermal growth factor receptor 2 (HER2)-positive recurrent disease with:
a. Distant metastases in patients with a performance status (PS) of 0-3 (NCCN 2A); OR
b. Unresectable locoregional recurrence or second primary with prior radiation therapy (NCCN 2A).
OVARIAN, FALLOPIAN TUBE AND PRIMARY PERITONEAL CANCER
1. Individual has a diagnosis of ovarian cancer or fallopian tube cancer or primary peritoneal cancer of endometroid (including grade 1 endometroid carcinoma), serous (including low-grade serous carcinoma), clear cell, mucinous carcinoma or carcinosarcoma histology; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a single-agent therapy for platinum-resistant persistent disease or recurrence in HER2- positive tumors [IHC 3+ or 2+] for:
a. Progression on primary, maintenance, or recurrence therapy (NCCN 2A); OR
b. Stable or persistent disease (if not on maintenance therapy) (NCCN 2A); OR
c. Complete remission and relapse <6 months after completing chemotherapy (NCCN 2A).
OCCULT PRIMARY DISEASE
1. Individual has a diagnosis of adenocarcinoma or carcinoma with HER2-positive [IHC 3+] tumors (not otherwise specified) occult primary disease; AND
2. Fam-trastuzumab deruxtecan-nxki will be used as a single agent in symptomatic individuals with performance status (PS) 1-2 or asymptomatic patients with PS 0 and aggressive disease that is metastatic or where surgical resection is likely to result in severe morbidity, and that has progressed on or following prior systemic treatment and has no satisfactory alternative treatment options for:
a. Axillary involvement in those with a prostate or post-prostatectomy if clinically indicated (NCCN 2A); OR
b. Lung nodules or breast marker-negative pleural effusion(NCCN 2A); OR
c. Resectable liver disease (NCCN 2A); OR
d. Peritoneal mass or ascites with non-ovarian histology (NCCN 2A); OR
e. Retroperitoneal mass of non-germ cell histology in selected individuals (NCCN 2A); OR
f. Unresectable liver disease or disseminated metastases(NCCN 2A); OR
2. Individual has a diagnosis of squamous cell carcinoma with HER2-positive [IHC 3+] tumors occult primary disease and fam-trastuzumab deruxtecan-nxki will be used as a single agent in symptomatic individuals with performance status (PS) 1-2 or asymptomatic individuals with PS 0 and aggressive disease for systemic therapy in individuals with multiple lung nodules, pleural effusion, or disseminated metastases that progressed on or following prior systemic treatment and have no satisfactory alternative treatment options (NCCN 2A).
Policy Guidelines
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
- 0 = Fully active, able to carry on all pre-disease performance without restriction
- 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework, office work
- 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
- 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
- 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
- 5 = Dead
The use of this drug is covered if a -approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosage and Administration
Dosing per Guidelines where applicable. For off-label indications, authorizations will not exceed 6.4 milligrams per kilogram of body weight every 3 weeks OR maximum recommended doses as outlined below unless medical literature supports a higher dose.
Breast Cancer – HER2 and HER2 low
The recommended dose is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21 day-cycle) until disease progression or unacceptable toxicity.
Gastric Cancer
The recommended dose 6.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cle) until disease progression or unacceptable toxicity.
NSCLC
The recommended dosage for lung cancer is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
Please see prescription guidance for recommended dose modifications, temporary interruption or treatment discontinuation in management of adverse reactions.
HER2-positive solid tumors
The recommended dose is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21 day-cycle) until disease progression or unacceptable toxicity.
Fam-trastuzumab deruxtecan-nxki (e.g., Enhertu) is available as 100 mg lyophilized powder in a single-dose vial.
Fam-trastuzumab deruxtecan-nxki (e.g., Enhertu) should be administered as an intravenous infusion by a healthcare professional.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Fam-trastuzumab deruxtecan-nxki (e.g., Enhertu), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, fam-trastuzumab deruxtecan-nxki (e.g., Enhertu), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificate of coverage.
Due to the detail of the policy statement, the document containing the coverage statements for dates prior to January 1, 2025 is not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com
