Use of trastuzumab (including Herceptin, Herzuma, Kanjinti, Ogivri, Ontruzant, and Trazimera) alone or in combination with chemotherapy is considered experimental and investigational for a list of tumor types for which efficacy has not been established. Examples include ampullary adenocarcinoma, bladder cancer, cancers of unknown primary, dermal adnexal cancer, hepatobiliary cancers (cholangiocarcinoma and gallbladder), intra-hepatic bile duct cancer, melanoma, neuroendocrine cervical cancer, non-small cell lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, penile cancer, prostate cancer, and vulvar cancer.

Certain ICD-10 diagnoses are identified in the policy as not covered for the listed CPB indications. Notable examples called out include C07 (parotid gland), C25.0–C25.9 (pancreas), C40.00–C41.9 (osteosarcoma), and C43.0–C43.9 (melanoma), along with select gynecologic and genitourinary cancer codes; these diagnoses are listed as exclusions when trastuzumab is requested for the CPB indications.

The NCCN clinical practice guideline for penile cancer (Version 1.2023) does not mention trastuzumab as a therapeutic option; therefore trastuzumab is not supported for penile cancer outside of exceptional circumstances or clinical trial enrollment.

In a phase II trial of single‑agent trastuzumab for advanced or recurrent endometrial carcinoma that required tumor HER2 over‑expression or amplification for eligibility, no major tumor responses were observed and neither HER2 over‑expression nor amplification was associated with improved PFS or overall survival. For this reason, single‑agent trastuzumab is generally not considered effective as standard therapy for endometrial carcinoma absent new corroborating evidence.

Single‑agent trastuzumab demonstrated limited clinical value in recurrent ovarian cancer studies because of the low frequency of HER2 over‑expression in screened populations and low objective response rates among those with 2+/3+ HER2 expression; thus routine use of trastuzumab monotherapy for recurrent ovarian cancer is not supported.

No explicit exclusions beyond those listed elsewhere are stated in the cited document sections; however, multiple tumor types are described as having limited or uncertain benefit from trastuzumab, indicating that coverage is dependent on documented HER2 positivity and supporting evidence for the specific tumor type.

The excerpts provided in these chunks do not list additional explicit coverage exclusions. See the policy history and full policy text for any administrative or plan‑specific exclusion language that may apply.

Requests for Herceptin, Herceptin Hylecta, Kanjinti, Ontruzant, or Trazimera are limited by Aetna's brand‑selection policy: these products are considered medically necessary only when the member has a documented contraindication, intolerance, or ineffective response to lower‑cost equivalent anti‑HER2 monoclonal antibodies (for example, Herzuma or Ogivri).

Use of trastuzumab in tumors without documented HER2 over‑expression or gene amplification (for example, IHC 0–1 without confirmatory FISH amplification) is not expected to be beneficial. Patient selection should be based on an FDA‑approved companion diagnostic (e.g., HercepTest) demonstrating HER2 over‑expression (IHC 2+ or 3+) or HER2 gene amplification prior to initiating trastuzumab.

Phase II studies and other trial data do not support routine use of trastuzumab in non‑small cell lung cancer: single‑agent trastuzumab showed minimal activity even in tumors with IHC 2+/3+ HER2 expression, and combinations with chemotherapy have not demonstrated improved outcomes sufficient to support standard use.

Evidence and guideline reviews for metastatic urothelial (bladder) cancer do not list trastuzumab as a therapeutic option, and clinical trials were limited by a low prevalence of HER2 over‑expression; thus trastuzumab is not supported as standard therapy for urothelial carcinoma outside of clinical trials or well‑defined HER2‑positive subsets.

The JACOB trial examined addition of pertuzumab to trastuzumab plus chemotherapy in first‑line HER2‑positive metastatic gastric or gastroesophageal junction cancer and did not show a statistically significant overall survival benefit (median OS 17.5 vs 14.2 months; HR 0.84; p = 0.057). Serious adverse events were more frequent in the pertuzumab arm. These results do not support routine use of dual HER2 blockade with pertuzumab and trastuzumab for first‑line metastatic gastric cancer based on that trial.

The provided excerpts do not contain explicit statements labeling particular uses as 'not medically necessary' beyond the experimental/investigational lists and brand‑selection constraints already described. Review the full policy for any additional 'not medically necessary' provisions.

This portion of the document does not list additional explicit 'not medically necessary' conditions. Refer to the full policy text for the complete set of not‑medically‑necessary statements and plan‑specific determinations.

References and prescribing information for trastuzumab products and for Herceptin Hylecta are cited in the policy. Providers should refer to the individual product prescribing information and the cited NCCN/clinical references for detailed dosing, administration, safety, and monitoring information when requesting authorization.

Prescribing information and randomized trial evidence are cited for Herceptin Hylecta and IV trastuzumab; these references imply that documentation of tumor HER2 over‑expression/amplification (e.g., IHC 2+/3+ or validated FISH) consistent with FDA‑approved indications is required to support use in indicated settings.