f oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise women of the potential hazard to the fetus resulting from Herceptin exposure during pregnancy and provide contraception counseling to women of childbearing potential. [see Use in Specific Populations (8.1), Patient Counseling Information (17)].
Herceptin use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non‑cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions [see Warnings and Precautions (5.2)]. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity.
In randomized, controlled clinical trials the per‑patient incidences of NCI CTC Grade 3–4 neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received Herceptin and those who did not. [see Adverse Reactions (6.1)]
Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy because these are the only patients studied and for whom benefit has been shown. Due to differences in tumor histopathology, use FDA-approved tests for the specific tumor type (breast or gastric/gastroesophageal adenocarcinoma) to assess HER2 protein overexpression and HER2 gene amplification. Tests should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results.
Several FDA‑approved commercial assays are available to aid in the selection of breast cancer and metastatic gastric cancer patients for Herceptin therapy. Users should refer to the package inserts of specific assay kits for information on the Intended Use, and the validation and performance of each assay.
Limitations in assay precision make it inadvisable to rely on a single method to rule out potential Herceptin benefit.
Treatment outcomes for adjuvant breast cancer (Studies 2 and 3) and for metastatic breast cancer (Study 5) as a function of IHC and FISH testing are provided in Tables 8 and 10.
Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using FDA-approved tests specifically for gastric cancers due to differences in gastric vs. breast histopathology, including incomplete membrane staining and more frequent heterogeneous expression of HER2 seen in gastric cancers. Study 7 demonstrated that gene amplification and protein overexpression were not as well correlated as with breast cancer. Treatment outcomes for metastatic gastric cancer (Study 7), based on HER2 gene amplification (FISH) and HER2 protein overexpression (IHC) test results are provided in Table 12.
The following adverse reactions are discussed in greate |
