Abstract 1269
Background
Exploration of neoadjuvant chemotherapy with anti-HER2 therapy to achieve higher pathological complete response (pCR) is important. We focused on trastuzumab emtansine (T-DM1), pertuzumab (P) and tailored response guided therapy in HER2+ primary breast cancer (cT1c–T3, cN0–N1, M0, tumor ≤ 7 cm).
Methods
This randomized phase II study evaluated efficacy and safety of 3 regimens, A) 6 cycles TCbHP, B) 4 cycles TCbHP followed by 4 cycles T-DM1+P, and C) 6 cycles T-DM1+P: responders to 4 cycles T-DM1+P were assigned to 2 more cycles [C1] or non-responders were assigned to 4 cycles FEC [C2] (Table). Responders: ≥30% decrease in tumor size (MRI) and Ki67 ≤10% or no cancer cells in core needle biopsy. ER(+) patients received anti-hormonal therapy concurrent to T-DM1+P. HER2, ER and Ki-67 were assessed in a central laboratory. Primary endpoint was pCR rate (yT0-is, yN0; centrally confirmed). Secondary endpoints were safety, ORR and breast conservation rate.
Results
A total of 206 patients were enrolled (Aug 2014-Feb 2016; full analysis set, n = 204). Patient characteristics were comparable among all groups (median age 53.0 y, post-menopause 53.9%, T2 70.6%, median tumor size 26 mm, N0 63.2%, ER(+) 57.8%). In group C, 80 (79.2%) patients continued T-DM1+P due to favorable response. pCR rate in group A, B, and C was 56.9%, 71.2%, and 57.4%. By exploratory analyses, pCR rate was higher for groups B and C1 than A in ER(+), but comparable in ER(-) patients. No significant differences in secondary endpoints. No treatment discontinuation due to AEs and similar drug-related SAE profile were seen among groups. Of specific mention: low drug-related alopecia in group C1 (5.0%) than A, B or C2 (81%–94%) and less febrile neutropenia in C1 (0%) than A, B or C2 (15%–33%).Table:
159PD Summary of response
| Variable | Group A (6-cycle TCbHP) % (n = 51) | Group B (4-cycle TCbHP switched to 4-cycle T-DM1+P) % (n = 52) | Group C1 (4-cycle T-DM1+P continued 2-cycle T-DM1+P) % (n = 80) | Group C2 (4-cycle T-DM1+P switched to 4-cycle FEC) % (n = 21) | Group C % (n = 101) |
|---|---|---|---|---|---|
| pCR rate, Overall | 56.9 (29/51) | 71.2 (37/52) | 62.5 (50/80) | 38.1 (8/21) | 57.4 (58/101) |
| pCR rate, ER (-) | 76.2 (16/21) | 73.9 (17/23) | 72.2 (26/36) | 33.3 (2/6) | 66.7 (28/42) |
| pCR rate, ER (+) | 43.3 (13/30) | 69.0 (20/29) | 54.5 (24/44) | 40.0 (6/15) | 50.8 (30/59) |
| ORR | 96.1 (49/51) | 86.5 (45/52) | 88.8 (71/80) | 85.7 (18/21) | 88.1 (89/101) |
| cCR | 47.1 (24/51) | 51.9 (27/52) | 38.8 (31/80) | 38.1 (8/21) | 38.6 (39/101) |
| Breast conservation rate | 52.0 (26/50) | 51.9 (27/52) | 54.4 (43/79) | 38.1 (8/21) | 51.0 (51/100) |
| Breast conservation rate from planned mastectomy | 34.4 (11/32) | 38.7 (12/31) | 36.7 (18/49) | 14.3 (2/14) | 31.7 (20/63) |
Dose was administered every 3 weeks as adjuvant therapy. ER (+) patients received concurrent endocrine therapy during T-DM1 treatment. ER, estrogen receptor; FEC, 5-fluorouracil/epirubicin/cyclophosphamide; ORR, overall response rate; pCR, pathological complete response; TCbHP, docetaxel/carboplatin/trastuzumab + pertuzumab; T-DM1+P, trastuzumab emtansine + pertuzumab
Conclusions
Addition of T-DM1+P to standard TCbHP regimen may be possibly superior to TCbHP. Tailored T-DM1+P is a promising approach with mostly equal efficacy and less toxicity compared to TCbHP.
Clinical trial identification
UMIN-CTR: UMIN000014649
Legal entity responsible for the study
Japan Breast Cancer Research Group
Funding
Japan Breast Cancer Research Group and Chugai Pharmaceutical Co., Ltd.
Disclosure
N. Masuda: Honorarium from Chugai and AstraZeneca. T. Takano, M. Toi: Funding from Chugai. Y. Ito: Funding from MSD, AstraZeneca, Novartis, Parexel, Chugai, and Lilly. H. Kasai: Consulting fee/honorarium from Chugai. T. Takasuka: Employee and stock options with Chugai. S. Morita: Consultancy for Chugai. All other authors have declared no conflicts of interest.