Phase III HannaH study of subcutaneous or intravenous trastuzumab for HER2-positive early breast cancer: Exploratory subgroup analyses of pathological complete response and 3-year event-free survival according to body weight and anti-drug antibody status

Background: HannaH (NCT00950300) compared subcutaneous and intravenous trastuzumab (Herceptin^® SC [H SC] and IV [H IV]) as neoadjuvant–adjuvant therapy for HER2-positive early breast cancer (EBC). Pathological complete response (pCR) with H SC was non-inferior to H IV and event-free survival (EFS, time from randomisation to local, regional or distant recurrence or progression, contralateral breast cancer or death) was similar after 2 years of treatment-free follow-up. Higher body-weight (wt) patients (pts) may have reduced H exposure from the 600mg SC fixed dose compared with wt-based IV dosing, possibly influencing efficacy; therefore, we explored pCR, total pCR (tpCR, absence of invasive neoplastic cells in ipsilateral lymph nodes and the breast) and EFS by wt. Effects of H anti-drug antibodies (ADAs) on EFS were also assessed.

Materials and Methods: Pts received four neoadjuvant docetaxel cycles followed by four cycles of 5-fluorouracil/epirubicin/cyclophosphamide concurrently with 3-weekly H SC or H IV (8mg/kg then 6mg/kg), then surgery followed by 10 cycles of adjuvant H SC or H IV. Samples for ADA tests were collected at baseline, during and after H SC and H IV treatment.

Results: A total of 297 pts were randomised to H SC and 299 to H IV. Intention-to-treat (ITT) populations were 294 and 297 pts, respectively; efficacy per protocol (EPP) populations, 260 and 263 pts. Median wts were 68kg (H SC) and 66kg (H IV). The highest wt decile was 90–137kg, overall. Efficacy by wt subgroups is shown in the table.

For ADA effects in the ITT population, hazard ratios between H SC and H IV for an EFS event were 0.69 (95%CI 0.26–1.86) and 1.00 (0.72–1.39) for ADA-positive and -negative pts, respectively. In the H SC arm, 3-year EFS rates were 80% and 75% for ADA-positive and -negative pts, respectively.

Conclusions: Efficacy (pCR/tpCR/EFS) of fixed-dose H SC was similar to wt-based H IV across wt subgroups and overall. H ADAs did not impact EFS. Efficacy of the H SC 600mg 3-weekly fixed dose, independent of pt wt, is confirmed for neoadjuvant–adjuvant therapy of HER2-positive EBC.

Conflict of interest: Ownership: AC-F: Roche shares. Advisory Board: CJ: Amgen. XP: Roche. Corporate-sponsored Research: CJ: Amgen. Other Substantive Relationships: BM: Roche, GSK, Novartis honoraria for advisory role and speeches. AC-F: Roche employee. SL: Roche contractor. MS: Genentech Inc employee.

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