Abstract 438
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
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| 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.