55O_PR - Phase III HannaH study of subcutaneous or intravenous trastuzumab for HER2-positive early breast cancer: Exploratory subgroup analyses of pathologi...

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Breast cancer
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Presenter Jin-Seok Ahn
Citation Annals of Oncology (2015) 26 (suppl_9): 16-33. 10.1093/annonc/mdv519
Authors C. Jackisch1, R. Hegg2, D. Stroyakovskiy3, J. Ahn4, B. Melichar5, S. Chen6, A. Crepelle-Flechais7, S. Lauer8, M. Shing9, X. Pivot10
  • 1Department Of Obstetrics And Gynecology & Breast Cancer And Gynecology Cancer Center, Sana Klinikum Offenbach GmbH, D-63069 - Offenbach/DE
  • 2Department Of Gynecology & Obstetrics, Hospital Pérola Byington, São Paulo/BR
  • 3Chemotherapeutic Department, City Clinical Oncology Hospital 62, Moscow/RU
  • 4Department Of Medicine, Samsung Medical Center and Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 5Department Of Oncology, Palacký University Medical School & Teaching Hospital, Olomouc/CZ
  • 6Department Of Surgery, Chang Gung Memorial Hospital, Taoyuan/TW
  • 7Global Pharma Development, F. Hoffmann-La Roche Ltd., Basel/CH
  • 8Biostatistics, F. Hoffmann-La Roche Ltd., CH-4070 - Basel/CH
  • 9Global Pharma Development, Genentech Inc., San Francisco/US
  • 10Chemotherapy - Oncology, CHU Jean Minjoz, 25030 - BesanÃÂon/FR

Abstract

Aim/Background

To explore pathological complete response (pCR), total pCR (tpCR, absence of invasive neoplastic cells in ipsilateral lymph nodes and the breast) and event-free survival (EFS, time from randomisation to local, regional or distant recurrence or progression, contralateral breast cancer or death) by weight (wt), and the effects of trastuzumab (Herceptin,® H) anti-drug antibodies (ADAs) on EFS in the HannaH study of subcutaneous (SC) and intravenous (IV) H as neoadjuvant–adjuvant therapy for HER2-positive early breast cancer (EBC).

Methods

Patients (pts) received four neoadjuvant docetaxel cycles followed by four cycles of 5-fluorouracil/epirubicin/cyclophosphamide concurrently with 3-weekly H SC (600 mg fixed dose) or H IV (8 mg/kg then 6 mg/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 68 kg (H SC) and 66 kg (H IV). The highest wt decile was 90–137 kg, overall. Efficacy by wt subgroups is shown in the table. Table 1

 

Wt quartiles, kg Wt decile, kg
Overall pts EPP <58 ITT <59 EPP ≥58 < 67 ITT ≥59 < 68 EPP ≥67 < 79 ITT ≥68 < 79 EPP/ITT ≥79 EPP/ITT 90–137
H route SC IV SC IV SC IV SC IV SC IV SC IV
pCR, EPP 45 (118/260) 41 (107/263) 54 (30/56) 37 (23/62) 44 (28/63) 43 (32/74) 46 (31/68) 41 (28/68) 40 (29/73) 41 (24/59) 40 (12/30) 44 (11/25)
% (n/N) ITT 42 (124/294) 37 (111/297) 48 (34/71) 36 (28/77) 44 (31/70) 39 (32/83) 41 (29/71) 37 (26/70) 37 (30/82) 37 (25/67) 35 (12/34) 38 (11/29)
tpCR, EPP 39 (102/260) 34 (90/263) 48 (27/56) 34 (21/62) 38 (24/63) 38 (28/74) 38 (26/68) 34 (23/68) 34 (25/73) 31 (18/59) 33 (10/30) 32 (8/25)
% (n/N) ITT 37 (108/294) 32 (94/297) 44 (31/71) 31 (24/77) 39 (27/70) 36 (30/83) 34 (24/71) 30 (21/70) 32 (26/82) 28 (19/67) 29 (10/34) 28 (8/29)
3-year EFS rate, % ITT 76 73 79 79 81 74 70 73 75 67 73 53

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 600 mg 3-weekly fixed dose, independent of pt wt, is confirmed for neoadjuvant–adjuvant therapy of HER2-positive EBC.

Clinical trial identification

NCT00950300

Disclosure

C. Jackisch: Advisory Board - Amgen; Corporate-sponsored Research – Amgen. B. Melichar: honoraria for advisory role and speeches for Roche, GSK and Novartis. A. Crepelle-Flechais: Ownership - Roche shares; Other Substantive Relationships - Roche employee. S. Lauer: Other Substantive Relationships - Roche contractor. M. Shing: Other Substantive Relationships - Genentech employee. All other authors have declared no conflicts of interest.