Dual HER2 blockade in the neoadjuvant and adjuvant treatment of HER2-positive breast cancer

Figures & data

Table 1 Summary of phase II and III trials using combination trastuzumab plus lapatinib in the neoadjuvant setting for HER2 positive breast cancer

Study/phase	Therapy	Patients enrolled	pCR rate (breast only)	pCR (breast + LN)	Rate of discontinuation	ORR
NeoALTTO/III^Citation30	A. L (1,500 mg) ×6 weeks → Paclitaxel + L ×12 weeks → surgery → FEC + L → L B. T ×6 weeks → Paclitaxel + T ×12 weeks → surgery → FEC + T → T C. T + L (1,000 mg → 750 mg) ×6 weeks → Paclitaxel + TL → surgery → FEC + TL → TL	T > 2 cm, N0–N3 455 patients (A: 154, B: 149, C: 152)	A. 24.7% (P=0.34) B. 29.5% C. 51.3% (P=0.0001)	A. 20% (P=0.13) B. 27.6% C. 46.8% (P=0.0007)	A. 33.8% B. 8.1% C. 39.5%	At surgery: (By Caliper) A. 74% (P=0.49) B. 70.5% C. 80.2% (P=0.049) At 6 weeks A. 52.6% (P<0.0001) B. 32% C. 67.1% (P<0.0001)
Cher-Lob/II^Citation33	A. Paclitaxel → FEC + T → surgery B. Paclitaxel → FEC + L (1,500 mg → 1,250 mg) → surgery C. Paclitaxel → FEC + T + L (1,000 mg → 750 mg) → surgery	Stage II–III A 121 patients (A: 36, B: 39, C: 46)	Not reported	A. 25% B. 26.3% C. 46.7% (P=0.019)	A. None B. 12 patients (17 interrupted) C. 8 patients (25 interrupted)	90% of total
^aCALGB-40601/II^Citation35	A. Paclitaxel + T ×16 weeks → surgery → AC → T B. Paclitaxel + T + L (750 mg) → surgery → AC → T C. Paclitaxel + L (1,500 mg – Closed early) → surgery → AC → T	Stage II–III, noninflammatory 305 patients (A: 120, B: 118, C: 67)	A. 40% B. 51% (P=0.11)	A. 43% B. 52% C. 29%	Not reported	Not reported
NSABP-B41/III^Citation34	A. AC → Paclitaxel + T → surgery → T B. AC → Paclitaxel + L (1,250 mg) → surgery → T C. AC → Paclitaxel + T + L (750 mg) → surgery → T	>2 cm palpable tumor 529 patients (A: 177, B: 171, C: 171)	A. 52.5% B. 53.2% (P=0.99 for Arm B vs A) C. 62% (P=0.095 for Arm C vs A)	A. 49.4% B. 47.4% (0.78) C. 60.2% (P=0.056)	A. 22% B. 32% C. 37%	Prior to surgery (By physical exam) A. 82% B. 69.9% (P=0.01) C. 76.8% (P=0.3)
TBCRC 006/II^Citation39	A. T + L (1,000 mg) → surgery B. T + L (1,000 mg) + letrozole (ER +) → surgery	>3 cm, or >2 cm + palpable LN Stage II–III 64 patients	A/B. 27% total (21% ER+, 36% ER−)	A/B. 22% total(18% ER +, 28% ER−)	Not reported	Not reported
^aTRIO US B07/II^Citation37	A. T ×21d → Docetaxel + Carboplatin + T → surgery B. L ×21d → Docetaxel + Carboplatin + L → surgery C. T + L ×21d → Docetaxel + Carboplatin + T + L → surgery	Stage I–III 128 patients (A: 34, B: 36, C: 58)	Not reported	A. 47% B. 25% C. 52%	A. None B. 28% C. 27%	Not reported

Notes: A, B, and C denote treatment arms A, B, and C. ^aDenotes that this study has only been presented in the form of an abstract.

Abbreviations: AC, doxorubicin and cyclophosphamide; ER, estrogen receptor; FEC, fluorouracil, epirubicin, cyclophosphamide; L, lapatinib; LN, lymph node; ORR, objective response rate; pCR, pathologic complete response; T, trastuzumab; HER2, human epidermal growth factor receptor 2; TL, trastuzumab and lapatinib; d, days; N, nodal stage.

Table 2 Summary of phase II trials using combination trastuzumab plus pertuzumab in the neoadjuvant setting for HER2 positive breast cancer

Study/phase	Therapy	Patients enrolled	pCR (breast only)	pCR (breast + LN)	Rate of discontinuation	ORR
NeoSphere/II^Citation45	A. T + docetaxel → surgery → FEC ×3 + T B.T + P + docetaxel → surgery → FEC ×3 + T C. T + P → surgery → docetaxel ×4 + T → FEC ×3 + T D. P + docetaxel → surgery → FEC ×3 + T	Stage II/III, including inflammatory cancer 417 patients (A: 107, B: 107, C: 107, D: 96)	A. 29% B. 45.8% (P=0.01) C. 16% D. 24%	A. 21.5% B. 39.3% C. 11.2% D. 17.7%	Not reported	Prior to surgery (complete or partial by physical exam) Breast Only A. 79.8% B. 88.1% C. 67.6% D. 71.4% Breast + LN A. 81.4% B. 88.0% C. 66.3% D. 73.9%
TRYPHAENA/II^Citation47	A. Carboplatin + docetaxel + T + P B. FEC → T + P + docetaxel C.FEC + T + P → T + P + docetaxel	Stage II/III, including inflammatory cancer 225 patients (A: 77, B: 75, C: 73)	A. 61.6% B. 57.3% C. 66.2%	A. 51.9% B. 45.3% C. 50.7%	Not reported	Prior to surgery (complete or partial) A. 89.6% B. 94.7% C. 91.8%

Note: A, B, and C denote treatment arms A, B, and C.

Abbreviations: FEC, fluorouracil, epirubicin, cyclophosphamide; L, lapatinib; LN, lymph node; ORR, objective response rate; P, Pertuzumab; pCR, pathologic complete response; T, trastuzumab; HER2, human epidermal growth factor receptor 2.

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