Neoadjuvant Chemotherapy and Targeted Therapy in Breast Cancer: Past, Present, and Future

Table 4

Trials investigating dose-dense and dose-intensified neoadjuvant chemotherapy.

Trial	Phase (𝑛)	Tumors	Treatment	Primary endpoint	Other outcomes	Ref.
GeparDuo	III (904)	T2-3 N0–2,	4 × DD ADoc, q14 + G-CSF versus 4 × AC → 4 × Doc, q21	pCR 7 versus 14% (𝑃<.001); (closed early because of pCR difference)	BCT 58 versus 63% (𝑃=.05); cORR 69 versus 79% (𝑃<.001); 5 y-EFS 65 versus 66% (𝑃=.66); 5 y-OS 81 versus 85% (𝑃=.24); trend for an improved DFS and OS for pts achieving a pCR (recurrence/death, 22/12% versus 29/17%, 𝑃=.37/.32)	[20, 59, 60]
AGO-1	III (668)	≥3 cm or cT4d	3 × IDD E → 3 × Pac, q14 versus 4 × E + 4 × Pac, q21; + 3 × CMF after S for all	pCR 18 versus 10% (𝑃=.008)	BCS 55 versus 50% (𝑃=.26); 5 y-DFS 70 versus 59% (HR 0.71, 𝑃=.011); 5 y-OS 83 versus 77% (HR 0.83, 𝑃=.041); no benefit for inflammatory BC; more nonhematologic toxicities, anemia, and thrombocytopenia, but similar neutropenia and infection rates	[22]
PREPARE	III (733)	≥2 cm or cT4d	3 × IDD E → 3 × Pac + G-CSF → CMF, q14 versus; 4 × EC → 4 × Pac, q21; ± DA	3 y-DFS 79 versus 76% (𝑃=.37)	3 y-OS 92 versus 88% (𝑃=.24); pCR 19 versus 13% (𝑃=.043); pCR associated with better DFS (𝑃=.001); 3 y-DFS DA + versus −: 74 versus 80% (𝑃=.061)	[23, 24]
SWOG 0012	III (372)	IIB-IIIB	5 × AC → 12 × Pac weekly versus 15 × A weekly + C daily p.o. + G-CSF	pCR 21 versus 24% (𝑃=.45)	No difference in DFS (HR 1.03, 𝑃=.87); no difference in OS (HR 1.19, 𝑃=.37)	[61]
MDACC	III (202)	IIA–IV	FAC q21 versus; DI FAC + G-CSF q18	pCR 9 versus 13% (𝑃=.35)	cORR 77 versus 92% (𝑃=.003); 5 y-OS 66 versus 67% (𝑃=.61); 5 y-DFS 56 versus 67% (𝑃=.12)	[62]

DD: dose dense; IDD: intensified dose dense; DI: dose intensified; ADoc: doxorubicin, docetaxel; AC: doxorubicin, cyclophosphamide; Doc: docetaxel; Pac: paclitaxel; CMF: cyclophosphamide, methotrexat, 5-FU; DA: darbepoetin alpha; C: cyclophosphamide; FAC: 5FU, doxorubicin, cyclophosphamide; A: doxorubicin.