Table 1.

Planned and ongoing high-impact randomized phase III trials in patients with HER2-overexpressing breast cancer

TrialDesignPopulationNo. of patientsTreatmentTrial endpointsData expected
TEACHPhase III, adjuvantStage I-IIIC, s/p neoadjuvant chemotherapy with an anthracycline, a taxane, and CMF3,000Placebo vs. L 1,500 mg/d for 12 monthsDFS, RFS, DRFS, OS, rate of CNS recurrence, QoL2012
ALTTO, BIG2–06/N063DPhase III, adjuvantStage I-IIIC, s/p neoadjuvant anthracycline-based chemotherapy (≥4 cycles)8,000Standard chemotherapy with (a) H, (b) L, (c) H × 12 weeks → L after 6-week washout, (d) H + L (all regimens for up to 1 year)DFS, OS, TTDR, TTR, CNS recurrence rate2013
ExteNETPhase III, adjuvantStage II-IIIC after adjuvant H for 1 year120Placebo vs. neratinibDFS2017
NEFERTTPhase III, MBCHER2+, no prior therapy for MBC1,200P + H vs. P + neratinibPFS, OS2012
Neo-ALTTOPhase III, neoadjuvantHER2+ >2 cm450(a) L × 6 weeks → L + P × 12 weeks vs. (b) H × 6 weeks → H + P × 12 weeks vs. (c) L + H × 6 weeks → H + L + P × 12 weeks; surgery; FEC × 3 → (a) L vs. (b) H vs. (c) H + L to complete 1 yearpCR rate, ORR, DFS, OS2011
NSABP B-41Phase III, neoadjuvantHER2+ >2 cm522AC × 4 → (a) P + H × 12 weeks vs. (b) P + L × 12 weeks vs. (c) P + H + L × 12 weekspCR rate, ORR, RFS, OS2010
CALGB 40601Phase III, neoadjuvantHER2+ stage II-IIIH + P vs. L + P vs. H + L + P → surgery → adjuvant chemotherapypCR rate, ORR, DFS, OS2011
Gepar-QuintoPhase III, neoadjuvantHER2+ requiring neoadjuvant chemotherapy2,547 (whole trial)EC → D → H vs. EC → D → LpCR rate2010
BETH, NSABP B-44Phase III, adjuvantHER2+, LN+, or high-risk LN−3,500TCH→ H (up to 1 year) vs. TCH → H + bevacizumab (up to 1 year)DFS, OS, RFS2012
BO22589Phase III, MBCHER2+, no prior therapy for MBC1,092H + taxane vs. T-DM1 vs. T-DM1 + pertuzumabPFS2012
EMILIAPhase III, MBCHER2+ LABC or MBC580T-DM1 vs. capecitabine + LPFS, OS, ORR2013
CLEOPATRAPhase III, MBCHER2+, no prior therapy for MBC800D + H + placebo vs. D + H + pertuzumabPFS2011
PHEREXAPhase II, MBCHER2+ MBC, second line after H450Capecitabine + H vs. capecitabine + H + pertuzumabPFS, TTP, TTF, ORR, CBR2015
BOLERO-1Phase III, MBCHER2+, no prior therapy for MBC717P + H vs. P + H + everolimusPFS, OS, ORR, CBR, TTR2012
BOLERO3Phase III, MBCHER2+, resistant to H572Vinorelbine + H vs. vinorelbine + H + everolimusPFS, OS, ORR, CBR2012

Abbreviations: H, herceptin; L, lapatinib; P, paclitaxel; D, docetaxel; TC, docetaxel, carboplatin; TCH, docetaxel, carboplatin, herceptin; DFS, disease-free survival; DRFS, distant relapse-free survival; OS, overall survival; QoL, quality of life; TTR, time to recurrence; TTDR, time to distant recurrence; DFS, disease-free survival; ORR, overall response rate; TTF, time to treatment failure; CBR, clinical benefit rate; AC, adriamycin/taxol; LABC, locally advanced breast cancer; CMF, cyclophosphamide, methotrexate, 5-fluoruracil; LN, lymph node; EC, epirubicin and cyclophosphamide