astuzumab concurrently with chemotherapy (docetaxel followed by 5FU, epirubicinand cyclophosphamide), followed by surgery and continued therapy with HERCEPTIN HYLECTA orintravenous trastuzumab as treated prior to surgery, for an additional 10 cycles, to complete 18 cycles of therapy.
HannaH was designed to demonstrate non-inferiority of treatment with HERCEPTIN HYLECTA versusintravenous trastuzumab based on co-primary PK and efficacy outcomes (trastuzumab Ctrough at pre-dose Cycle8, and pCR rate at definitive surgery, respectively) [see Clinical Pharmacology 12.3]. EFS and OS were amongother outcomes eva luated in this study. The majority of patients were white (69%) and the median age was 50years (range: 24-81).
The analysis of the efficacy co-primary outcome, pCR, defined as absence of invasive neoplastic cells in thebreast, resulted in rates of 45.4% (95% CI: 39.2%, 51.7%) in the HERCEPTIN HYLECTA arm and 40.7% (95%CI: 34.7, 46.9) in the intravenous trastuzumab arm.
Table 8:
Summary of Pathological Complete Response (pCR) (HannaH)
HERCEPTIN HYLECTA
(n=260)
Intravenous Trastuzumab
(n=263)
pCR (absence of invasive neoplastic cells in breast
[ypT0/is])
118 (45.4%) 107 (40.7%)
Exact 95% CI for pCR Rate * (39.2; 51.7) (34.7; 46.9)
Difference in pCR (SC minus IV arm) 4.70
95% CI for Difference in pCR† (-4.0; 13.4) * CI for one sample binomial using Pearson-Clopper methodApproximate 95% CI for difference of two rates using Hauck-Anderson methodWith a median follow-up exceeding 70 months, no difference in EFS and OS was observed in the final analysisbetween patients who received intravenous trastuzumab and those who received HERCEPTIN HYLECTA.
SafeHER
The SafeHER study (NCT01566721) was a prospective, two-cohort, non-randomized, multinational, open-labelstudy designed to assess the overall safety and tolerability of HERCEPTIN HYLECTA with chemotherapy in1864 patients with HER2-positive breast cancer. The secondary objectives include the eva luation of DFS and OS.
HER2-positivity was defined as IHC 3+ or ISH+. Patients received a fixed dose of 600 mg HERCEPTINHYLECTA every 3 weeks for a total of 18 cycles throughout the study. HERCEPTIN HYLECTA treatment wasinitiated either sequentially with chemotherapy, concurrently with chemotherapy, or without adjuvantchemotherapy, or in combination with neoadjuvant chemotherapy followed by trastuzumab therapy. The majorityof treated patients were white (76%) and the median age was 54 years (range: 20-88).
In the primary safety analysis (median follow-up 23.7 months), no new safety signals were identified forHERCEPTIN HYLECTA. Safety and tolerability results, including in lower weight patients, were consistent withthe known safety profile for HERCEPTIN HYLECTA and intravenous trastuzumab.
In the ITT population (n=1867), 126 patients (7%) had a DFS event (recurrence, contralateral invasive breastcancer or death) and 28 patients (1.5%) had an OS event at the time of clinical cut-off.
Intravenous Trastuzumab
The safety and efficacy of intravenous trastuzumab in women receiving adjuvant chemotherapy for HER2overexpressing breast cancer were eva luated in an integrated analysis of two randomized, open-label, clinicaltrials (Studies NSABP B31 and NCCTG N9831) with a total of 4063 women at the protocol-specified final
overall survival analysis, a third randomized, open-label, clinical trial (HERA Study) with a total of 3386wo |
