What is the best pharmacotherapeutic strategy for HER-2 positive breast cancer?

Figures & data

Table 1. Selection of the most influential randomized clinical trials of anti-HER2-treatments in the metastatic setting.

Author	Setting	Treatment	N of Pts	Median PFS or TTP (months)	Median OS (months)
Slamon [4]	MBC, I line	Chemotherapy (Paclitaxel or cyclophosphamide + an anthracycline) + trastuzumab vs Chemotherapy alone	234	7.4 vs. 4.6 P < 0.001	25.1 vs. 20.3 P = 0.046
Marty [5]	MBC, I line	Trastuzumab + docetaxel vs docetaxel alone	186	11.7 vs. 6.1 P = 0.0001	31.2 vs. 22.7 P = 0.0325
Geyer [6]	MBC, trast. resistant	Lapatinib capecitabine vs capecitabine	399	8.4 vs. 4.4 P < 0.001	18.8 vs. 16.2 P = 0.210
Von Minckwitz [7]	MBC, trast resistant	Trastuzumab capecitabine vs capecitabine	156	8.2 vs. 5.6 P = 0.0338	25.5 vs. 20.4 0.257
Swain [8]	MBC, I line	Docetaxel, trastuzumab and pertuzumab vs Docetaxel and trastuzumab	808	18.7 vs. 12.4 P < 0.001	56.5 vs. 40.8 P < 0.01
Verma [9]	MBC, trast. resistant	T-DM1 vs lapatinib and capecitabine	991	9.6 vs. 6.4 P < 0.001	30.9 vs. 25.1 P < 0.001
Krop [10]	MBC, trast. and lap. resistant	T-DM1 vs TPC	602	6.2 vs. 3.3 P < 0.0001	22.7 vs. 15.8 P < 0007

MBC, metastatic breast cancer; PFS, progression-free survival; TTP, time to progression; OS, overall survival.

Table 2. Summary of the most influencing randomized trials in the adjuvant setting.

Author	Arms	N. patients	Timepoint	(i)DFS (%)	OS (%)
Cameron [11]	Chemotherapy Chemotherapy → 1y T Chemotherapy→ 2y T	5012	10 years	63 69* 69*	73 79* 80*
Perez [12]	AC→P AC→PT→T	4046	10 years	62.2 73.7*	75.2 84.0*
Slamon [13]	AC→D AC→DT→T DCT→T	3222	10 years	67.9 74.6* 73.0*	78.7 85.9* 83.3*
Von Minckwitz [14]	A(E)C→PT→T or DCT Same as above plus Ptz.	4804	3 years	93.1 94.2**	96.7 96.2
Martin [15]	Placebo Neratinib 1 y	2840 completing prior adj. trast.	5 years	87.7 90.2***	N.A.

T, trastuzumab; (i)DFS, disease-free survival or invasive disease-free survival; OS, overall survival; AC, doxorubicin and cyclophosphamide; P, paclitaxel; D, docetaxel, C; carboplatinum; E; epi-doxorubicin; Ptz, pertuzumab; N.A., non available.

*Difference with the comparator, trastuzumab-free arm is statistically significant.

**Difference with the comparator, pertuzumab-free arm is statistically significant.

***Difference over placebo is statistically significant.

Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–792.

 PubMed Web of Science ®Google Scholar

Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005;23(19):4265–4274.

 PubMed Web of Science ®Google Scholar

Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355(26):2733–2743.

 PubMed Web of Science ®Google Scholar

von Minckwitz G, Du Bois A, Schmidt M, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03–05 study. J Clin Oncol. 2009;27(12):1999–2006.

 PubMed Web of Science ®Google Scholar

Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724–734.

 PubMed Web of Science ®Google Scholar

Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–1791.

 PubMed Web of Science ®Google Scholar

Krop IE, Kim S-B, Gonzalez-Martin A, et al. Final overall survival results from TH3RESA, a randomised phase 3 study of trastuzumab emtansine (T-DM1) versus treatment of physician’s choice in patients with previously treated HER2-positive metastatic breast cancer. Lancet Oncol. 2017;18(6):743–754.

 PubMed Web of Science ®Google Scholar

Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075):1195–1205.

 PubMed Web of Science ®Google Scholar

Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014;32(33):3744–3752.

 PubMed Web of Science ®Google Scholar

Slamon D, Eiermann W, Robert N, et al. Abstract S5-04: ten year follow-up of BCIRG-006 comparing doxorubicin plus cyclophosphamide followed by docetaxel (AC→T) with doxorubicin plus cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2+ early breast cancer. Cancer Res. 2016;76(4 Suppl):S5–S04.

 Google Scholar

von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122–131.

 PubMed Web of Science ®Google Scholar

Martin M, Holmes FA, Ejlertsen B, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12):1688–1700.

 PubMed Web of Science ®Google Scholar