mplification ratio ≥ 2.0 by Dako HER2 FISH PharmDx™ test kit. Only limited data were available for patients whose breast cancer was positive by FISH and 0 or 1+ by IHC.
Assessment of HER2 status should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance, including use of sub- optimally 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.
5.9 Extravasation
In KADCYLA clinical studies, reactions secondary to extravasation have been observed. These reactions, observed more frequently within 24 hours of infusion, were usually mild and comprised erythema, tenderness, skin irritation, pain, or swelling at the infusion site. Specific treatment for KADCYLA extravasation is unknown. The infusion site should be closely monitored for possible subcutaneous infiltration during drug administration.
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the label:
•Hepatotoxicity [See Warnings and Precautions (5.1)]
•Left Ventricular Dysfunction [See Warnings and Precautions (5.2)]
•Embryo-Fetal Toxicity [See Warnings and Precautions (5.3)]
•Pulmonary Toxicity [See Warnings and Precautions (5.4)]
•Infusion-Related Reactions, Hypersensitivity Reactions [See Warnings and Precautions (5.5)]
•Thrombocytopenia [See Warnings and Precautions (5.6)]
•Neurotoxicity [See Warnings and Precautions (5.7)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical trials, KADCYLA has been eva luated as single-agent in 884 patients with HER2-positive metastatic breast cancer. The most common (frequency ≥ 25%) adverse drug reactions (ADRs) seen in 884 patients treated with KADCYLA were fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, increased transaminases, and constipation.
The ADRs described in Table 6 were identified in patients with HER2-positive metastatic breast cancer treated in a randomized trial (Study 1) [see Clinical Studies (14.1)]. Patients were randomized to receive KADCYLA or lapatinib plus capecitabine. The median duration of study treatment was 7.6 months for patients in the KADCYLA-treated group and 5.5 months and 5.3 months for patients treated with lapatinib and capecitabine, respectively. Two hundred and eleven (43.1%) patients experienced ≥ Grade 3 adverse events in the KADCYLA-treated group compared with 289 (59.2%) patients in the lapatinib plus capecitabine-treated group. Dose adjustments for KADCYLA were permitted [see Dosage and Administration (2.2)]. Thirty-two patients (6.5%) discontinued KADCYLA due to an adverse event, compared with 41 patients (8.4%) who discontinued lapatinib, and 51 patients (10.5%) who discontinued capecitabine due to an adverse event. The most common adverse events leading to KADCYLA withdrawal were thrombocytopenia and increased transaminases. Eighty patients (16.3%) treated w |
