Table 4 Landmark clinical trials in the development of HER2 inhibitors
From: Clinical development of targeted and immune based anti-cancer therapies
Drug Name | Clinical Trial ID | Trial Name | Population | Comparator | Year | Sponsor | Phase | N | Median OS (months) | Median PFS (months) |
|---|---|---|---|---|---|---|---|---|---|---|
HER2 inhibitors | ||||||||||
 Trastuzumab (Herceptin®) | ||||||||||
  Trastuzumab (4 mg/kg followed by 2 mg/kg) + doxorubicin + cyclophosphamide | NCT00004067 |  | Breast cancer (HER2+) | Doxorubicin + cyclophosphamide + paclitaxel | 2000–2020 | NSABP Foundation Inc | 3 | 42,130 | NA | NA |
  Trastuzumab (8 mg/kg followed by 6 mg/kg) + chemotherapy | NCT01998906 |  | Breast cancer (HER2+) | Chemotherapy | 2002–2012 | Hoffmann-La Roche | 3 | 330 | NA | NA |
  Trastuzumab (4 mg/kg followed by 2 mg/kg) + docetaxel | Marty et al. (2005) | M77001 | Breast cancer (HER2+) | Docetaxel | 2000–2005 | Hoffmann-La Roche | 2 | 186 | 31.2 vs 22.7 | 11.7 vs 6.1 |
  Trastuzumab (4 mg/kg followed by 2 mg/kg) + lapatinib | NCT00320385 |  | Breast cancer (HER2+) | Lapatinib | 2005–2010 | GlaxoSmithKline | 3 | 296 | 51.6 vs 39 (weeks) | 12 vs 8.1 (weeks) |
  Trastuzumab (8 mg/kg followed by 6 mg/kg) + fluorouracil + cisplatin + capecitabine | NCT01041404 | ToGA Study | HER2+ advanced gastric cancer | Fluorouracil + Cisplatin + Capecitabine | 2005–2010 | Hoffmann-La Roche | 3 | 584 | 11.1 vs 13.8 | 5.5 vs 6.7 |
  Trastuzumab (4 mg/kg followed by 2 mg/kg) + chemotherapy | NCT00021255 |  | Breast cancer (HER2+) | Chemotherapy | 2001–2014 | Sanofi | 3 | 3222 | 78.9 vs 86 | NA |
  Trastuzumab (2 mg/kg i.v. weekly, or 6 mg/kg i.v. every 3 weeks) + chemotherapy | NCT00448279 | THOR | Breast cancer (HER2+) | Chemotherapy | 2007–2010 | Hoffmann-La Roche | 3 | 58 | 19.1 vs 26.7 | 9.7 vs 9.4 |
 T-DM1 (Trastuzumab Emtansine/ Kadcyla®) | ||||||||||
  T-DM1 (3.6 mg/kg/3w) | NCT00829166 | EMILIA | Breast cancer (HER2+) | Lapatinib + Capecitabine | 2009–2015 | Hoffmann-La Roche | III | 991 | 30.9 vs 25.1 | 9.6 vs 6.4 |
  T-DM1 (3.6 mg/kg/3w) | NCT01419197 | TH3RESA | Breast cancer (HER2+) | Physician’s choice | 2011–2015 | Hoffmann-La Roche | III | 602 | 22.7 vs 15.8 | 6.2 vs 3.3 |
 Pertuzumab (Perjeta®) | ||||||||||
  Pertuzumab (420 mg/3w) + trastuzumab + docetaxel | NCT00567190 | CLEOPATRA | Breast cancer (HER2+) | Trastuzumab and Docetaxel | 2008–2018 | Hoffmann-La Roche | III | 808 | 56.5 vs 40.8 | 18.7 vs 12.4 |
  Pertuzumab (420 mg/3w) + trastuzumab + capecitabine | NCT01026142 | PHEREXA | Breast cancer (HER2+) | Trastuzumab + capecitabine | 2010–2017 | Hoffmann-La Roche | III | 452 | 37.2 vs 28.1 | 11.1 vs 9.0 |
  Pertuzumab (420 mg/3w) + trastuzumab + chemotherapy | NCT01358877 | APHINITY | Breast cancer (HER2+) | Trastuzumab + chemotherapy | 2011–2016 | Hoffmann-La Roche | III | 4804 | NR | 8.7 vs 7.1% |
  Pertuzumab + T-DM1 | NCT01120184 | MARIANNE | Breast cancer (HER2+) | T-DM1 + Placebo | 2010–2016 | Hoffmann-La Roche | III | 1095 | 51.8 vs 53.7 | 15.2 vs 14.1 |
 Lapatinib (Tykerb®) | ||||||||||
  Lapatinib (1250 mg/d) + capecitabine | NCT00078572 |  | Metastatic breast cancer (HER2+) | Capecitabine | 2004–2010 | GSK | III | 408 | 10.4 vs 8.0 | 8.4 vs 4.4 |
  Lapatinib (1500 mg/d) | NCT00073528 |  | Metastatic breast cancer | Letrozole | 2003–2018 | Novartis | III | 1285 | 33.3 vs 32.3 | 8.1 vs 3.0 |
  Lapatinib (1500 mg/d) | NCT00374322 | TEACH | Early stage breast cancer | Placebo | 2006–2013 | GSK | III | 3166 | NR | NR |