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©2014 Baishideng Publishing Group Inc.
World J Clin Oncol. Aug 10, 2014; 5(3): 440-454
Published online Aug 10, 2014. doi: 10.5306/wjco.v5.i3.440
Published online Aug 10, 2014. doi: 10.5306/wjco.v5.i3.440
Table 1 Selected clinical trials in the adjuvant setting for human epidermal growth factor receptor-2 positive breast cancer
Drug or studyname | Populationincluded | No. ofpatients | Comparison | Medianfollow-up | DFS | OS | CHF/Drop LVEF | Ref. |
Trastuzumab (H) | ||||||||
NCCTG N9831 | LN (+) or | 1087 | AC → T vs | 71.8% (5-yr) | 88.4% (5-yr) | 0%/0% | Perez et al[14] | |
high risk LN (-) | 949 | AC → T → H (52 wk) vs AC | 72 mo | 80.1% (5-yr) | 89.7% (5-yr) | 2.2%/7% | ||
954 | → TH (H then 40 wk) | 84.4% (5-yr) | 91.9% (5-yr) | 1.5%/3.6% | ||||
HERA | LN (+) or | 1552 | Std QT → H (52 wk) vs | 96 mo | 75.9% (5-yr) | 86.9% (5-yr) | 1%/7.2% | Goldhirsch et al[16] |
high risk LN (-) | 1553 | Std QT → H (104 wk) vs | 76.5% (5-yr) | 88.7% (5-yr) | 0.8%/4.1% | |||
1697 | Std QT → Observation | 70.0% (5-yr) | 84.5% (5-yr) | 0.1%/0.9% | ||||
FINHER | LN (+) or | 58 | Docetaxel → FEC vs | 62 mo | 74.1% (5-yr) | 82.0% (5-yr) | 1.7%/10.5% | Joensuu et al[18] |
high risk LN (-) | 58 | Vinorelbine → FEC vs | 72.0% (5-yr) | 82.8% (5-yr) | (QT only) | |||
54 | Docetaxel + H → FEC vs | 92.5% (5-yr) | 94.4% (5-yr) | 0.9%/6.8% | ||||
61 | Vinorelbine + H → FEC | 75.2% (5-yr) | 88.4% (5-yr) | (QT + H) | ||||
BCIRG 006 | LN (+) or | 1073 | AC → Docetaxel vs | 65 mo | 75% (5-yr) | 87% (5-yr) | 0.7%/11.2% | Slamon et al[19] |
high risk LN (-) | 1074 | AC → Docetaxel + H vs | 84% (5-yr) | 92% (5-yr) | 2.0%/18.6% | |||
1075 | TCH | 81% (5-yr) | 91% (5-yr) | 0.4%/9.4% | ||||
PACS 04 | LN (+) | 260 | FE100C or ED75 → Obser vs | 62 mo | 77.9% (3-yr) | 96% (3-yr) | 0.3%/14.2% | Spielmann et al[20] |
268 | FE100C or ED75 → H | 80.9% (3-yr) | 95% (3-yr) | 1.5%/35.4% | ||||
PHARE | HER-2 (+) early breast cancer | 1690 | Std QT → H (26 wk) vs | 42.5 mo | 91.1% (2-yr) | 96.1% (2-yr) | 5.7% (both) | Pivot et al[21] |
1690 | Std QT → H (52 wk) | 93.8% (2-yr) | 94.5% (2-yr) | 1.9% (both) | ||||
Lapatinib (L) | ||||||||
TEACH | Stage I-IIIc – H naïve | 1230 (HER-2 +) | Std QT → L (52 wk) vs | 47.4 mo | 87% (4-yr) | 94% (4-yr) | 3.0% (both) | Goss et al[22] |
1260 (HER-2 +) | Std QT → Observation | 48.3 mo | 83% (4-yr) | 94% (4-yr | 3.0% (both) |
Table 2 Selected clinical trials in the neo-adjuvant setting for human epidermal growth factor receptor-2 positive breast cancer
Study | Neo-adjuvant chemotherapy | No. of patients | Pathological completeresponse (%) | Comments | Ref. |
Trastuzumab (H) | |||||
MD Anderson Group | T → FEC vs T → FEC + H | 19 vs 23 | 26% (95%CI: 9%-51%) vs 65% (95%CI: 43%-84%) | Probably the first study to emphasize better pCR with H | Buzdar et al[24] |
The NOAH Trial | A + T → T → CMF vs A + T → T → CMF + H | 117 HER-2 (+) vs 118 HER-2 (+) | 22% (95%CI: not reported) vs 43% (95%CI: not reported) | Not originally designed to test the effects of neoadjuvance | Gianni et al[26] |
The TECHNO Trial | EC → TH | 217 | 38.7% (95%CI: 32%-45%) | Suggest pCR correlate with DFS | Untch et al[27] |
The Z1041 Trial | FEC → TH vs T + H → FEC + H | 138 vs 142 | 56.5% (95%CI: 48%-65%) vs 54.2% (95%CI: 46%-62%) | Concurrent use of H with anthracyclines is not better | Buzdar et al[28] |
The HannaH Trial | Doc + H (SQ) → FEC + H vs Doc + H (IV) → FEC + H | 260 vs 263 | 45.4% (95%CI: 39%-52%) vs 40.7% (95%CI: 35%-47%) | H can be administered subcutaneously | Ismael et al[30] |
Lapatinib(L) +/- (H) | |||||
The GeparQuinto Trial | ECH → TH vs ECL → TL | 309 vs 311 | 30.3% (95%CI: 25%-36%) vs 22.7% (95%CI: 18%-28%) | Lapatinib is less effective that H | Untch et al[31] |
The NeoALLTO Trial | TH vs TL vs THL | 149 vs 154 vs 152 | 29.5% (22%–37%) vs 24.7% (22% -37%) vs 51.3% (43%-59%) | Suggested that combination H + L could be quite effective | Baselga et al[32] |
The NSABP B-41 Trial | AC → TH or TL or THL | 181 vs 174 vs 174 | 52.5% (50%-59.5%) vs 53.2% (45%-60%) vs 62.0% (54%-69%) | H + L no better. All patients received anthracyclines | Robidoux et al[33] |
Pertuzumab (P) | |||||
The NeoSphere Trial | Do + H vs Do + P + H vs Do + P vs P + H | 107 vs 107 vs 107 vs 96 | 29.0% (21%-38.5%) vs 45.8% (36%-56%) vs 24.0% (16%-34%) vs 16.8% (10%-25%). | Combination P + H result in better pCR. | Gianni et al[34] |
The Tryphaena Trial (Abstract Only) | FEC + HP → Do + HP vs FEC → Do + HP vs TCHP | 223 patients in total | 62% vs 57% vs 66% | TCH + P is an active combination | N/A |
Table 3 Selected clinical trials in metastatic human epidermal growth factor receptor-2 positive breast cancer
Drug or study name | Population included | No. ofpatients | Comparison | MedianOS (mo) | MedianTTP (mo) | ORR | 1-yr Survival | Ref. |
Single agents | ||||||||
Trastuzumab (H) | Phase II, first line, MBC | 114 | None-2 doses of H used | 24.4 | 3.8 | 26% (18%-34%) | N/A (approximat- ely 65%) | Vogel et al[45] |
Ado-trastuzumab | Phase II, refractory MBC | 110 | None | N/A | 6.9 (4.2–8.4) | 34% (26%-44%) | N/A | Krop et al[48] |
Anti-HER-2 + QT | ||||||||
H + Paclitaxel (T) | Phase III, first line, MBC | 469 | QT (AC or T) + H vs QT | 25.1 vs 20.3 | 7.4 vs 4.6 | 50% vs 32% | 78% vs 67% | Slamon et al[44] |
Cont. Anti-HER-2 after failing 1st line | ||||||||
Lapatinib (L) | Phase III, failed to H | 324 | Cape + L vs Cape alone | N/A | 8.4 vs 4.4 | 22% vs 14% | N/A (approximat- ely 60%) | Geyer et al[54] |
EMILIA Trial (Ado-trastuzumab) | Phase III, MBC who failed TH | 991 | Ado-T vs Cape + L | 30.9 vs 25.1 | 9.6 vs 6.4 | 43.6% vs 30.8% | 85% vs 78% | Verma et al[55] |
Dual Anti-HER-2 | ||||||||
CLEOPATRA | Phase III, first line, MBC | 808 | Do + H + P vs Do + H | Not reached | 18.5 vs 12.4 | 80% vs 69% | N/A (approximat- ely 90%-95%) | Baselga et al[57] |
Lap + Trastuzumab | Phase III, failed to H | 296 | L + H vs L alone | 11.8 vs 8.9 | 2.75 vs 1.85 | 10% vs 7% | 70% vs 36% | Blackwell et al[59] |
H + Pertuzumab (P) | Phase II, failed to H | 66 | None-H + P single arm | N/A | 5.5 | 24.20% | N/A | Baselga et al[61] |
Anti-HER-2 + AI | ||||||||
Anastrozole + H | Phase III, HR and HER-2 positive, 1st line in MBC | 207 | Anastrozole + H vs Anastrozole alone | 28.5 vs 23.9 | 4.8 vs 2.4 | 20% vs 6.8% | N/A (approximat- ely 78%) | Kaufman et al[63] |
Letrozole + L | Same | 219 | Letrozole + L vs Letrozole alone | 33.3 vs 32.3 | 8.2 vs 3.0 | 28% vs 15% | N/A | Johnston et al[64] |
- Citation: Jr GR, Canton ED, Vega ML, Greco M, Sr GR, Valsecchi ME. Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions. World J Clin Oncol 2014; 5(3): 440-454
- URL: https://www.wjgnet.com/2218-4333/full/v5/i3/440.htm
- DOI: https://dx.doi.org/10.5306/wjco.v5.i3.440