observed in theclinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may notreflect the rates observed in practice.
The safety of HERCEPTIN HYLECTA administered subcutaneously has been established in the HannaH andSafeHER studies conducted in patients with HER2 overexpressing breast cancer. The safety of intravenoustrastuzumab has been established in studies H0648g and H0649g conducted in patients with HER2overexpressing metastatic breast cancer.
Adjuvant Breast Cancer
HannaH
HannaH was a randomized, open-label study to compare the pharmacokinetics, efficacy, and safety of HERCEPTIN HYLECTA compared to intravenous trastuzumab in women with HER2-positive breast cancer.
Patients randomized to the HERCEPTIN HYLECTA arm received a dose of 600 mg HERCEPTIN HYLECTAevery 3 weeks throughout the treatment phase. Patients were treated for 8 cycles in combination withchemotherapy (docetaxel followed by 5FU, epirubicin and cyclophosphamide), then underwent surgery, andcontinued HERCEPTIN HYLECTA to complete 18 cycles of therapy. The median age of patients was 50 (range:25-81 years), all patients were female, and a majority of patients were white (67%). The median number ofHERCEPTIN HYLECTA cycles received was 18 (range 1-18).
The most common adverse reactions of any grade (occurring in ≥10% of patients) with HERCEPTIN HYLECTAwere alopecia (63%), nausea (49%), ARRs (48%), neutropenia (44%), diarrhea (34%), asthenia (25%), fatigue(24%), vomiting (23%), myalgia (21%), decreased appetite (20%), stomatitis (19%), arthralgia (18%), headache
(17%), rash (16%), constipation (14%), radiation skin injury (14%), pyrexia (12%), cough (12%), anemia (11%),dyspnea (11%), incision site pain (11%), peripheral sensory neuropathy (11%), leukopenia (10%), mucosalinflammation (10%), hot flush (10%), upper respiratory tract infection (10%).
The most common Grade ≥3 adverse reactions (occurring in >1% of patients) in the HERCEPTIN HYLECTAarm were neutropenia (30%), febrile neutropenia (6%), leukopenia (4%), diarrhea (3%), hypertension (2%),irregular menstruation (2%), alopecia (1%), nausea (1%), granulocytopenia (1%), vomiting (1%), amenorrhea(1%), and cellulitis (1%). Adverse reactions leading to interruption of any study drug in the HERCEPTINHYLECTA arm occurred in 34% of patients; 31% of patients had these events during the neoadjuvant phase ofthe study with concurrent chemotherapy and 9% of patients had these events during the adjuvant phase. Overall,the most common (> 1%) were neutropenia (21%), leukopenia (2.4%), ALT increase (1.7%), pyrexia (1.7%),anemia (1%), bronchitis (1%), and left ventricular dysfunction (1%). Adverse reactions that led to discontinuationof any study drug in the HERCEPTIN HYLECTA arm (>1 patient) were left ventricular dysfunction (2%).
The incidence of ARRs in the HERCEPTIN HYLECTA arm was 48% and was 37% in the intravenoustrastuzumab arm. Five (2%) patients in the HERCEPTIN HYLECTA arm experienced a Grade 3 ARR. Three ofthe events in the HERCEPTIN HYLECTA arm occurred on the day of study drug administration when docetaxeltreatment was administered concurrently. The most commonly reported ARRs in the HERCEPTIN HYLECTAarm (≥5% of patients) were rash, pruritus, erythema, cough and dyspnea. Grade 1 and 2 injection-site reactions
(ISRs) occurred in 10% of patients in the HERCEPTIN HYLECTA arm. The most common ISRs were injectionsi |
