Total pathologic complete response (tpCR) and event-free survival (EFS) with subcutaneous (SC) or intravenous (IV) trastuzumab in HER2-positive early breast cancer (EBC).

Background: HannaH (NCT00950300) compared SC and IV trastuzumab (Herceptin SC [H SC] and IV [H IV]) as neoadjuvant–adjuvant therapy for HER2-positive EBC; the co-primary endpoints, pCR and serum trough concentration, were non-inferior between H SC and H IV. Prior studies have indicated that pCR is reasonably likely to predict for long-term efficacy outcomes in patients (pts) with EBC, and tpCR (absence of invasive neoplastic cells in ipsilateral lymph nodes and the breast) is considered more likely to be predictive than pCR. Methods: HannaH is a phase III, open-label, multicenter, randomized trial. Pts received 4 cycles of neoadjuvant docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly H SC (600 mg fixed dose) or H IV (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, pts received 10 cycles of adjuvant H SC or H IV to complete 1 year of therapy. In an exploratory analysis, we used Cox regression to assess the correlation between the secondary endpoints tpCR and EFS (time from randomization to local, regional, or distant recurrence, contralateral breast cancer, or death). EFS rates per subgroup were estimated using the Kaplan–Meier (K–M) method. Results: In all, 297 pts were randomized to the H SC arm and 299 to the H IV arm; intent-to-treat (ITT) populations were 294 and 297 pts, respectively. At 40 months’ median follow-up, Cox regression indicated that pts in the ITT population who achieved tpCR had a reduced risk of an EFS event compared with those who did not: H SC arm hazard ratio (HR) = 0.38 (95% CI, 0.22–0.65); H IV arm HR = 0.32 (95% CI, 0.18–0.60). Results were similar between arms: treatment-tpCR interaction P = 0.67. Three-year EFS rates according to tpCR are shown in the Table. Results were consistent for pCR and the efficacy per protocol population. Conclusions: In each of HannaH’s two treatment arms, H SC or H IV, tpCR correlated with improved long-term efficacy outcomes (EFS) in pts who received neoadjuvant–adjuvant therapy for HER2-positive EBC. Clinical trial information: NCT00950300