Table 3

Chemotherapy approaches: dose density, neoadjuvant approaches, post-neoadjuvant

StudyTrial nameSettingPrimary outcomeMedian follow-upDFS controlDFS gainDFS HR*OS controlOS gain (%)OS HR*pCRESMO-MCBS V.1.1Reference
dd studies
 AC-P q21 vs q14INT C9741/CALGB 9741Node+DFS36 months75.00%7.00%0.74 (0.59–0.93)90.00%2.000.69 (0.50–0.93)C23
 EC-P q21 vs q14AGONode+EFS62 months62.00%8.00%0.72 (0.59–0.87)77.00%5.000.76 (0.59– 0.97)B24
 (F)EC-P q21 vs q14GIMNode+DFS7 years76.00%5.00%0.77 (0.65–0.92)89.00%5.000.65 (0.51– 0.84)B25
 Meta-analysis—dd vs regular schedule2 weekly vs 3 weekly (same regimen)DFS and OS10 years28.30%4.30%0.83 (0.76–0.91)Breast cancer mortality 19.6%1.800.86 (0.77–0.95)C26
 Meta-analysis—dd vs regular schedulePooled-analysis—all dd and sequentialDFS and OS10 years32.00%3.60%0.65 (0.81–0.89)Breast cancer mortality 19.6%2.700.87 (0.82–0.92)C26
 Meta-analysis—dd vs regular schedulePooled analysis—all dd and sequentialDFS and OS10 yearsAll-cause mortality 25.5%3.000.87 (0.82–0.91)B26
 dd vs regular scheduleStratified for HR statusDFS and OSVariable 2–10 yearsAll0.84 (0.77–0.91)0.85 (0.79–0.93)B27
 dd vs regular scheduleStratified for HR statusDFS and OSVariable 2–10 yearsHR−ve0.80 (0.69–0.92)B27
 dd vs regular scheduleStratified for HR statusDFS and OSVariable 2–10 yearsHR+ve0.93 (0.82–1.05)NEB27
Post-neoadjuvant chemotherapy
 Capecitabine vs placeboCREATE—XResidual disease after neoadjuvant therapyDFS3.6 yearsAll 67.6%6.50%0.70 (0.53–0.92)83.60%5.600.59 (0.39–0.90)*A28
 Capecitabine vs placeboCREATE—XResidual disease after neoadjuvant therapyDFS3.6 yearsTriple negative 56.1%13.70%0.58 (0.39–0.87)70.30%8.500.52 (0.30–0.90)A28
 Capecitabine vs placeboCREATE—XResidual disease after neoadjuvant therapyDFS3.6 yearsHR + /HER2-neg 73.4%3.00%0.81 (0.55–1.17)90.00%3.400.73 (0.38–1.14)NEB28
Neoadjuvant carboplatin
 Neoadjuvant Peg-A+P+Bev vs Peg-A+P+Bev+CarboGeparSixtoTriple negativepCR35 months76.10%9.70%0.56 (0.33–0.96)41% vs 56.8% (ss)A29
 P vs P + carboplatinBRIGHTNESSTriple negativepCR41% vs 56.8%C30
 P + carboplatin vs P + carboplatin + veliparibBRIGHTNESSTriple negativepCR58% vs 53% (ns)NEB30
 Neoadjuvant AC+P ± carboplatinCALBG 40603Triple negativepCR3 years71.00%5.00%0.84 (0.58–1.22)85.00%−4.001.15 (0.74–1.79)41% vs 54% (ss)NEB31
 Neoadjuvant AC-P ± bevacizumabCALBG 40603Triple negativepCR3 years72.00%3.00%0.80 (0.55–1.17)81.00%4.000.76 (0.49–1.19)44% vs 52% (ss)NEB31
Neoadjuvant other agents
 D+AC vs DG+ACNSABP-B40HER2-negativepCR4.7 years72.80%1.10%0.90 (0.67–1.19)80.90%4.800.73 (0.51–1.04)32.7% vs 31.8% (ns)NEB11
 D+AC vs DX+ACNSABP-B40HER2-negativepCR4.7 years72.80%−0.20%1.01 (0.77–1.33)80.90%0.600.96 (0.68–1.32)32.7% vs 29.7% (ns)NEB11
 Above regimens ± BevNSABP-B40HER2-negativepCR4.7 years72.80%4.00%0.80 (0.63–1.01)80.90%0.65 (0.49–0.88)28.2 vs 34.5% (ss)B/C11
 EC+D vs EC+D+BevGeparQuintoNeoadjuvant —all subtypespCR3.8 years81.50%−2.00%1.03 (0.84–1.25)88.70%2.000.97 (0.75–1.26)14.9 vs 18.4% (ss)NEB83
 P-EC vs Nab-P-ECGeparSeptoNeoadjuvant —all subtypespCR29% vs 38.4% (ss)NEB33
  • Chart blanks—relevant variables not available in manuscript.

  • *HR values in parentheses refer to 95% CI.

  • A, doxorubicin; Bev, bevacizumab; C, cyclophosphamide; Carbo, carboplatin; D, docetaxel; DFS, disease-free survival; E, epirubicin; EFS, event-free survival; ESMO-MCBS, The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale; F, fluorouracil; G, gemcitabine; HER2-neg, HER2-negative; HR+, hormone-positive; iDFS, invasive disease-free survival; Nab-P, Nab-paclitaxel; nc, not statistically significant; NEB, no evaluable benefit; OS, overall survival; P, paclitaxel; pCR, pathological complete response; Peg-A, pegylated doxorubicin; q21, every 21 days; ss, statistically signifcant; V, veliparib; X, capecitabine.