| mechanism | treatment | Demonstrated benefit and harm | k | | | |
|---|
| angiogenesis inhibitors | bevacizumab | versus no bevacizumab No demonstrated result for efficacy bevacizumab + capecitabine inferior to capecitabine in terms of adverse events grade 3 in RIBBON-I (Robert) on top capecitabine, 2009 bevacizumab + capecitabine inferior to capecitabine in terms of hypertension (grade 3) in RIBBON-I (Robert) on top capecitabine, 2009 bevacizumab + taxanes inferior to taxanes in terms of adverse events grade 3 in RIBBON-I (Robert) on top Tax or anthra, 2009 bevacizumab + taxanes inferior to taxanes in terms of serious adverse events in RIBBON-I (Robert) on top Tax or anthra, 2009 bevacizumab + taxanes inferior to taxanes in terms of hypertension (grade 3) in RIBBON-I (Robert) on top Tax or anthra, 2009 bevacizumab + taxanes inferior to taxanes in terms of permanent discontinuation in RIBBON-I (Robert) on top Tax or anthra, 2009 | 9 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| E2100 (Miller), 2007 | bevacizumab + taxanes vs taxanes | progression-free survival (PFS) 0.56 [0.32; 0.97] objective response 2.20 [1.68; 2.88] | | proteinuria (grade 3) ∞ [NaN; ∞] left ventricular systolic dysfunction (grade 2 or 3) 2.84 [0.30; 27.21] overall survival (OS) 0.86 [0.49; 1.52] hypertension (grade 3) ∞ [NaN; ∞] arterial/venous thromboembolism (grade 3) 1.52 [0.50; 4.59] gastrointestinal perforation (grade 3) ∞ [NaN; ∞] bleeding (grade 3) ∞ [NaN; ∞] high-grade congestive heart failure 7.58 [0.95; 60.32] permanent discontinuation 1.14 [0.86; 1.52] treatment-related deaths 1.90 [0.17; 20.82] | | AVADO (Miles) 15mg , 2009 | bevacizumab + docetaxel vs docetaxel | progression-free survival (PFS) 0.69 [0.54; 0.88] objective response 1.22 [1.10; 1.36] | | overall survival (OS) 0.92 [0.62; 1.37] | | RIBBON-I (Robert) on top capecitabine, 2009 | bevacizumab + capecitabine vs capecitabine | objective response 1.50 [1.09; 2.05] | adverse events grade 3 1.62 [1.21; 2.17] hypertension (grade 3) 10.20 [2.49; 41.74] | venous thromboembolic event (grade 3) 1.42 [0.61; 3.31] arterial thromboembolic event 1.00 [0.25; 3.94] proteinuria (grade 3) ∞ [NaN; ∞] left ventricular systolic dysfunction (grade 2 or 3) 2.99 [0.36; 24.63] overall survival (OS) 0.85 [0.40; 1.82] progression-free survival (PFS) 0.68 [0.34; 1.34] serious adverse events 1.28 [0.92; 1.79] gastrointestinal perforation (grade 3) NaN [NaN; NaN] bleeding (grade 3) 0.50 [0.03; 7.91] high-grade congestive heart failure 6.91 [0.91; 52.33] permanent discontinuation 1.00 [0.63; 1.58] treatment-related deaths 0.60 [0.18; 1.93] | | RIBBON-I (Robert) on top Tax or anthra, 2009 | bevacizumab + taxanes vs taxanes | objective response 1.36 [1.09; 1.68] | adverse events grade 3 1.70 [1.32; 2.19] serious adverse events 1.49 [1.10; 2.01] hypertension (grade 3) 9.78 [2.39; 40.07] permanent discontinuation 3.22 [1.80; 5.77] | venous thromboembolic event (grade 3) 0.82 [0.30; 2.21] arterial thromboembolic event 1.96 [0.22; 17.39] proteinuria (grade 3) ∞ [NaN; ∞] left ventricular systolic dysfunction (grade 2 or 3) 1.47 [0.59; 3.64] overall survival (OS) 1.03 [0.48; 2.20] progression-free survival (PFS) 0.77 [0.38; 1.56] gastrointestinal perforation (grade 3) 2.45 [0.29; 20.80] bleeding (grade 3) ∞ [NaN; ∞] treatment-related deaths 0.65 [0.23; 1.85] | | AVF2119g (Miller) cape, 2005 | bevacizumab + capecitabine vs capecitabine | objective response 2.17 [1.34; 3.52] | | pulmonary embolism (grade 3) 0.94 [0.19; 4.60] overall survival (OS) 1.07 [0.54; 2.11] progression-free survival (PFS) 0.98 [0.49; 1.96] cardiomyopathy (grade 3) 1.88 [0.17; 20.56] high-grade congestive heart failure 2.52 [0.53; 12.00] | | Burstein, 2005 | bevacizumab + methotrexate vs methotrexate | | | objective response 3.09 [0.75; 12.74] arterial/venous thromboembolism (grade 3) ∞ [NaN; ∞] | | RIBBON-2 (Brufsky), 2009 | bevacizumav + CT vs CT alone | objective response 1.33 [1.03; 1.73] | | overall survival (OS) 0.90 [0.46; 1.77] progression-free survival (PFS) 0.78 [0.43; 1.43] high-grade congestive heart failure ∞ [NaN; ∞] | | AVADO (Miles) 7.5mg, 2010 | bevacizumab + docetaxel vs docetaxel | | | overall survival (OS) 1.05 [0.81; 1.36] progression-free survival (PFS) 0.86 [0.72; 1.03] | | Martin bevacizumab, 2011 | bevacizumab + paclitaxel vs paclitaxel | | | left ventricular systolic dysfunction (grade 2 or 3) NaN [NaN; NaN] progression-free survival (PFS) 0.79 [0.33; 1.90] objective response 1.24 [0.91; 1.69] serious adverse events 0.75 [0.46; 1.23] hypertension (grade 3) 6.49 [0.81; 51.71] permanent discontinuation 1.70 [0.89; 3.23] treatment-related deaths 0.31 [0.03; 2.92] |
| Trial | Treatments | Patients | Method |
|---|
| E2100 (Miller), 2007 | paclitaxel + bevacizumab 10 mg/kg iv every 2 weeks (n=368) vs. paclitaxel 90 mg per square meter of body-surface area on days 1, 8, and 15 every 4 weeks (n=354) | patients with metastatic breast cancer not previously treated | open Parallel groups Sample size: 368/354 Primary endpoint: PFS FU duration: | | AVADO (Miles) 15mg , 2009 | Docetaxel + bevacizumab 7.5 mg/kg iv every 3 weeks (n=-9) vs. (n=-9) | first-line treatment of HER2-negative metastatic breast cancer | Sample size: -9/-9 Primary endpoint: PFS FU duration: | | RIBBON-I (Robert) on top capecitabine, 2009 | Capecitabine + bevacizumab 15 mg/kg iv every 3 weeks (n=-9) vs. capecitabine (Cape; 2,000 mg/m(2) for 14 days), (n=-9) | irst-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer | double-blind Sample size: -9/-9 Primary endpoint: PFS FU duration: | | RIBBON-I (Robert) on top Tax or anthra, 2009 | Taxanes or anthracyclines + bevacizumab 15 mg/kg iv every 3 weeks (n=-9) vs. taxane (Tax) -based (nab-paclitaxel 260 mg/m(2), docetaxel 75 or 100 mg/m(2)), or anthracycline (Anthra) -based (doxorubicin or epirubicin combinations [doxorubicin/cyclophosphamide, epirubicin/cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide, o (n=-9) | irst-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer | Sample size: -9/-9 Primary endpoint: PFS FU duration: | | AVF2119g (Miller) cape, 2005 | capecitabine + bevacizumab 15 mg/kg iv every 3 weeks (n=232) vs. capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks (n=230) | patients with metastatic breast cancer previously treated with an anthracycline and a taxane | open Parallel groups Sample size: 232/230 Primary endpoint: PFS FU duration: | | Burstein, 2005 | Methotrexate + cyclophosphamide + bevacizumab 10 mg/kg iv every 2 weeks (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: response FU duration: | | RIBBON-2 (Brufsky), 2009 | addition of BV to chemotherapies used as second-line treatment for MBC (n=-9) vs. chemo+placebo (n=-9) | second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer | open Parallel groups Sample size: -9/-9 Primary endpoint: investigator-assessed PFS FU duration: | | AVADO (Miles) 7.5mg, 2010 | bevacizumab 7.5mg/kg every 3 weeks plus docetaxel (n=248) vs. placebo plus docetaxel (n=241)
| first-line treatment of HER2-negative metastatic breast cancer
| double-blind Sample size: 248/241 Primary endpoint: PFS FU duration:
| | Martin bevacizumab, 2011 | bevacizumab 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle (n=-9) vs. control (n=-9) | patients with HER2-negative locally recurrent or metastatic breast cancer | open design Sample size: -9/-9 Primary endpoint: FU duration: |
|
| angiogenesis inhibitors | ceritinib | versus endocrine therapy alone No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Hyams | cediranib + fulvestrant vs fulvestrant | | | |
| Trial | Treatments | Patients | Method |
|---|
| Hyams | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| angiogenesis inhibitors | motesanib | versus no bevacizumab No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Martin (motesanib), 2011 | motesanib + paclitaxel vs paclitaxel | | | |
| Trial | Treatments | Patients | Method |
|---|
| Martin (motesanib), 2011 | motesanib 125 mg orally once per da (n=91) vs. placebo (n=94)
| patients with untreated HER2-negative metastatic breast cancer
| double-blind Sample size: 91/94 Primary endpoint: FU duration:
|
|
| CDK (cyclin-dependent kinase) inhibitor | abemaciclib | versus endocrine therapy alone Abemaciclib +nsAI superior to nsAI in terms of progression free survival in MONARCH 3, 2017 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MONARCH 3, 2017 | Abemaciclib +nsAI vs nsAI | progression free survival 0.54 [0.41; 0.72] median not reached vs. 14.7 mo Demonstrated | | |
| Trial | Treatments | Patients | Method |
|---|
| MONARCH 3, 2017 | Abemaciclib (LY2835219) + nonsteroidal aromatase inhibitors (nSAI) (n=493) vs. Placebo + NSAI (n=0) | Postmenopausal Women With Hormone Receptor-Positive, HER2-Negative Locoregionally Recurrent or Metastatic Breast Cancer With No Prior Systemic Therapy in This Disease Setting
| double-blind Parallel groups Sample size: 493/0 Primary endpoint: PFS FU duration: |
|
| CDK (cyclin-dependent kinase) inhibitor | palbociclib | versus endocrine therapy alone palbociclib + letrozole superior to letrozole alone in terms of progression free survival in PALOMA-2, 2016 (first line patients) palbociclib + fulvestrant superior to fulvestrant alone in terms of progression free survival in PALOMA 3, 2015 (2nd line patients) | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PALOMA-2, 2016 | palbociclib + letrozole vs letrozole alone | progression free survival 0.58 [0.46; 0.73] median 24.8 mo vs. 14.5 mo Demonstrated | | | | PALOMA 3, 2015 | palbociclib + fulvestrant vs fulvestrant alone | progression free survival 0.42 [0.32; 0.56] median 9.2 mo vs. 3.8 mo Demonstrated | | | | PALOMA 1/TRIO-18, 2015 | palbociclib + letrozole vs letrozole alone | progression free survival 0.49 [0.32; 0.75] | | |
| Trial | Treatments | Patients | Method |
|---|
| PALOMA-2, 2016 | PD-0332991, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).) (n=666) vs. Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously (n=0) | postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic disease | double-blind Parallel groups Sample size: 666/0 Primary endpoint: PFS FU duration: | | PALOMA 3, 2015 | palbociclib (125 mg per day orally for 3 weeks,
followed by 1 week off) and fulvestrant (500 mg
intramuscularly per standard of care every 14 days
for the first three injections and then every
28 days) (n=347) vs. placebo and fulvestrant (n=174) | women with HR+, HER2 negative metastatic breast cancer whose disease has progressed after prior endocrine therapy | double-blind Parallel groups Sample size: 347/174 Primary endpoint: investigator-assessed PFS FU duration: | | PALOMA 1/TRIO-18, 2015 | continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles (n=84) vs. continuous oral letrozole 2.5 mg daily (n=81) | postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease | open-label Parallel groups Sample size: 84/81 Primary endpoint: investigator-assessed progression-free survival FU duration: phase 2 |
|
| CDK (cyclin-dependent kinase) inhibitor | ribociclib | versus endocrine therapy alone ribociclib (LEE011) + letrozole superior to letrozole alone in terms of progression free survival in MONALEESA-2, 2016 (first line patients) | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MONALEESA-2, 2016 | ribociclib (LEE011) + letrozole vs letrozole alone | progression free survival 0.56 [0.43; 0.72] median not reached vs. 14.7 mo Demonstrated | | |
| Trial | Treatments | Patients | Method |
|---|
| MONALEESA-2, 2016 | ribociclib
(600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per
day) (n=334) vs. placebo + letrozole (n=334) | postmenopausal women with HR-positive, HER2-negative recurrent
or metastatic breast cancer who had not received previous systemic therapy
for advanced disease | double-blind Parallel groups Sample size: 334/334 Primary endpoint: PFS FU duration: 18 months OS data were not mature at the time of the PFS interim analysis.
No treatment
crossover was allowed. |
|
| drugs interfering with tubulin | ixabepilone | versus No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Sparano, 2010 | ixabepilone (on top capecitabine) vs no ixabepilone | | | overall survival 0.90 [0.78; 1.03] | | Thomas, 2007 | ixabepilone (on top capecitabine) vs no ixabepilone | PFS 0.75 [0.64; 0.88] | | overall survival 0.90 [0.77; 1.05] |
| Trial | Treatments | Patients | Method |
|---|
| Sparano, 2010 | ixabepilone (40 mg/m(2) intravenously on day 1) plus capecitabine (2,000 mg/m(2) orally on days 1 through 14) given every 21 days (n=-9) vs. capecitabine alone (2,500 mg/m(2) on the same schedule) given every 21 days (n=-9) | patients with metastatic breast cancer previously treated with anthracycline and taxanes | open Parallel groups Sample size: -9/-9 Primary endpoint: overall survival FU duration: | | Thomas, 2007 | ixabepilone 40 mg/m(2) intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle (n=752) vs. capecitabine alone 2,500 mg/m(2) on days 1 through 14 of a 21-day cycle (n=0) | patients with metastatic breast cancer progressing after anthracycline and taxane treatment | open Parallel groups Sample size: 752/0 Primary endpoint: progression-free survival FU duration: |
|
| HER2 inhibitors | pertuzumab | versus anti-HER2 antibody + taxanes No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CLEOPATRA, 2012 | pertuzumab + trastuzumab +docetaxel vs trastuzumab + docetaxel | OS 0.68 [0.56; 0.83] PFS 0.62 [0.51; 0.75] | | | | neoSphere (Group B), 2012 | pertuzumab + trastuzumab +docetaxel vs trastuzumab + docetaxel | | | |
| Trial | Treatments | Patients | Method |
|---|
| CLEOPATRA, 2012 | pertuzumab plus trastuzumab plus docetaxel (n=406) vs. placebo plus trastuzumab plus docetaxel (n=402) | patients with HER2-positive metastatic breast cancer | double-blind Parallel groups Sample size: 406/402 Primary endpoint: progression-free survival FU duration: | | neoSphere (Group B), 2012 | pertuzumab and trastuzumab
plus docetaxel (n=107) vs. trastuzumab plus docetaxel (n=107) 4 arms:
A) trastuzumab plus docetaxel;
B) pertuzumab and trastuzumab
plus docetaxel
C)pertuzumab and trastuzumab
D) pertuzumab plus docetaxel | women with locally advanced, inflammatory, or early HER2-positive breast cancer | Sample size: 107/107 Primary endpoint: FU duration: |
|
| HER2 inhibitors | trastuzumab emtansine | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| EMILIA, 2012 | trastuzumab emtansine vs lapatinib plus capecitabine | OS 0.68 [0.55; 0.85] PFS 0.65 [0.55; 0.77] | | |
| Trial | Treatments | Patients | Method |
|---|
| EMILIA, 2012 | Trastuzumab emtansine (n=496) vs. lapatinib plus capecitabine (n=495) | patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane | Parallel groups Sample size: 496/495 Primary endpoint: FU duration: |
|
| HER2 inhibitors | trastuzumab emtansine | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| TH3RESA, 2014 | trastuzumab emtansine vs usual care | PFS 0.53 [0.42; 0.66] | | |
| Trial | Treatments | Patients | Method |
|---|
| TH3RESA, 2014 | trastuzumab emtansine (n=404) vs. physician's choice (n=198) | patients with progressive HER2-positive advanced breast cancer who had received two or more HER2-directed regimens in the advanced setting | open-label Parallel groups Sample size: 404/198 Primary endpoint: progression-free survival (PFS) and overall survival FU duration: |
|
| histone deacetylase (HDAC) inhibitors | entinostat | versus endocrine therapy alone No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| ENCORE 301, 2013 | entinostat 5 mg once per week + exemestane 25 mg daily (n=64) vs. exemestane plus placebo (n=66) | Postmenopausal women with ER+ advanced breast cancer progressing on a nonsteroidal aromatase inhibitor | Sample size: 64/66 Primary endpoint: FU duration: |
|
| kinase inhibition | lapatinib | versus endocrine therapy alone lapatinib + letrozole superior to letrozole alone in terms of PFS in Johnston (EGF30008) , 2009 lapatinib + letrozole inferior to letrozole alone in terms of SAE in Johnston (EGF30008) , 2009 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Johnston (EGF30008) , 2009 | lapatinib + letrozole vs letrozole alone | PFS 0.71 [0.53; 0.96] Demonstrated | SAE 2.00 [1.57; 2.55] | OS 0.78 [0.57; 1.07] |
| Trial | Treatments | Patients | Method |
|---|
| Johnston (EGF30008) , 2009 | daily letrozole (2.5 mg orally) plus lapatinib (1,500 mg orally) (n=1286) vs. letrozole (n=0) | hormone receptor-positive metastatic breast cancer | double-blind Parallel groups Sample size: 1286/0 Primary endpoint: FU duration: |
|
| kinase inhibition | lapatinib | versus taxanes alone No demonstrated result for efficacy lapatinib + paclitaxel inferior to paclitaxel alone in terms of SAE in Di Leo, 2008 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Di Leo, 2008 | lapatinib + paclitaxel vs paclitaxel alone | | SAE 1.65 [1.16; 2.35] | OS 0.86 [0.69; 1.08] PFS 0.90 [0.75; 1.08] |
| Trial | Treatments | Patients | Method |
|---|
| Di Leo, 2008 | first-line therapy with paclitaxel 175 mg/m(2) every 3 weeks plus lapatinib 1,500 mg/d (n=579) vs. paclitaxel (n=0) | first-line treatment for metastatic breast cancer | double-blind Parallel groups Sample size: 579/0 Primary endpoint: TTP FU duration: |
|
| kinase inhibition | sorafenib | versus CT alone No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Schwartzberg, 2013 | sorafenib + gemcitabine or capecitabine vs gemcitabine or capecitabine alone | PFS 0.64 [0.44; 0.93] | | OS 1.01 [0.71; 1.44] | | Baselga, 2012 | sorafenib + capecitabine vs capecitabine alone | PFS 0.58 [0.41; 0.82] | | OS 0.86 [0.61; 1.22] |
| Trial | Treatments | Patients | Method |
|---|
| Schwartzberg, 2013 | sorafenib (400 mg, twice daily) (n=-9) vs. placebo (n=-9) | patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Baselga, 2012 | - or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day (n=-9) vs. capecitabine alone (n=-9) | HER2-negative locally advanced or metastatic breast cancer | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: PFS FU duration: |
|
| kinase inhibition | sorafenib | versus taxanes alone No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Gradishar, 2013 | sorafenib + paclitaxel vs paclitaxel alone | | | OS 1.02 [0.71; 1.46] PFS 0.79 [0.56; 1.11] |
| Trial | Treatments | Patients | Method |
|---|
| Gradishar, 2013 | paclitaxel (90mg/m(2), weekly, intravenously, 3 weeks on/1 week off) plus sorafenib (400mg, orally, twice daily) (n=-9) vs. paclitaxel (90mg/m(2), weekly, intravenously, 3 weeks on/1 week off) (n=-9) | first-line therapy in patients with HER2-negative advanced breast cancer | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: |
|
| monoclonal antibody | trastuzumab | versus No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Blackwell, 2010 | trastuzumab + lapatinib vs lapatinib alone | | | | | Gasparini, 2006 | trastuzumab + paclitaxel vs paclitaxel alone | | | | | Marty, 2005 | trastuzumab + docetaxel vs docetaxel alone | | | | | Slamon, 2001 | trastuzumab + standard chemotherapy vs standard chemotherapy alone | | | | | von Minckwitz, 2009 | trastuzumab + capecitabine vs capecitabine alone | | | |
| Trial | Treatments | Patients | Method |
|---|
| Blackwell, 2010 | lapatinib + trastuzumab (n=-9) vs. lapatinib alone (n=-9) | women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer | Sample size: -9/-9 Primary endpoint: progression-free survival FU duration: | | Gasparini, 2006 | trastuzumab + weekly paclitaxel (n=-9) vs. weekly paclitaxel (n=-9) | patients with advanced breast cancer overexpressing HER-2. | Sample size: -9/-9 Primary endpoint: FU duration: | | Marty, 2005 | (n=-9) vs. (n=-9) | patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment | Sample size: -9/-9 Primary endpoint: FU duration: | | Slamon, 2001 | standard chemotherapy plus trastuzumab (n=-9) vs. standard chemotherapy alone (n=-9) | women with metastatic breast cancer that overexpressed HER2 | Sample size: -9/-9 Primary endpoint: FU duration: | | von Minckwitz, 2009 | trastuzumab + capecitabine (n=-9) vs. capecitabine alone (n=-9) | Patients with HER-2-positive breast cancer that progresses during treatment with trastuzumab | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| monoclonal antibody | trastuzumab | versus endocrine therapy alone No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Huober, 2012 | trastuzumab + letrozole vs letrozole alone | | | | | TAnDEM (Kaufman), 2009 | trastuzumab + anastrozole vs anastrozole alone | | | |
| Trial | Treatments | Patients | Method |
|---|
| Huober, 2012 | letrozole plus trastuzumab (n=-9) vs. letrozole alone (n=-9) | patients with HER2-positive, hormone-receptor-positive metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | TAnDEM (Kaufman), 2009 | anastrozole (1 mg/d orally) with trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression (n=-9) vs. anastrozole (n=-9) | postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| mTOR inhibitor | everolimus | versus No demonstrated result for efficacy everolimus inferior to sunitinib in terms of PFS in RECORD 3, 2014 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| RECORD-1, 2008 | everolimus vs placebo | PFS 0.30 [0.22; 0.40] | | OS 0.83 [0.50; 1.37] | | RECORD 3, 2014 | everolimus vs sunitinib | | PFS 1.40 [1.14; 1.71] | |
| Trial | Treatments | Patients | Method |
|---|
| RECORD-1, 2008 | everolimus 10 mg once daily (n=272) vs. placebo (n=138) | Patients with metastatic renal cell carcinoma which had progressed on sunitinib, sorafenib, or both | Sample size: 272/138 Primary endpoint: PFS FU duration: | | RECORD 3, 2014 | everolimus (n=238) vs. sunitinib (n=233) | patients with metastatic renal cell carcinoma | Cross over Sample size: 238/233 Primary endpoint: FU duration: |
|
| mTOR inhibitor | everolimus | versus CT everolimus + trastuzumab + vinorelbine superior to trastuzumab + vinorelbine alone in terms of PFS in BOLERO-3, 2014 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| BOLERO-3, 2014 | everolimus + trastuzumab + vinorelbine vs trastuzumab + vinorelbine alone | PFS 0.78 [0.65; 0.94] Demonstrated | | |
| Trial | Treatments | Patients | Method |
|---|
| BOLERO-3, 2014 | daily everolimus (5 mg/day) plus weekly trastuzumab (2 mg/kg) and vinorelbine (25 mg/m(2)) in 3-week cycles (n=284) vs. placebo plus trastuzumab plus vinorelbine, (n=285) | women with HER2-positive, trastuzumab-resistant, advanced breast carcinoma who had previously received taxane therapy | double-blind Parallel groups Sample size: 284/285 Primary endpoint: PFS by local assessment FU duration: |
|
| mTOR inhibitor | everolimus | versus endocrine therapy alone everolimus + exemestane superior to exemestane alone in terms of PFS in BOLERO-2, 2011 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| BOLERO-2, 2011 | everolimus + exemestane vs exemestane alone | PFS 0.43 [0.35; 0.53] Demonstrated | | OS 0.89 [0.73; 1.09] | | TAMRAD , 2012 | everolimus + tamoxifen vs tamoxifen alone | OS 0.45 [0.24; 0.84] Time to progression (TTP) 0.54 [0.36; 0.81] | | |
| Trial | Treatments | Patients | Method |
|---|
| BOLERO-2, 2011 | everolimus and exemestane (n=485) vs. exemestane and placebo (n=239) | patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). | double-blind Parallel groups Sample size: 485/239 Primary endpoint: progression-free survival FU duration: | | TAMRAD , 2012 | tamoxifen 20 mg/d plus everolimus 10 mg/d (n=54) vs. tamoxifen 20 mg/d alone (n=57) | postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, AI-resistant mBC | open-label Sample size: 54/57 Primary endpoint: FU duration: |
|
| mTOR inhibitor | temsirolimus | versus No demonstrated result for efficacy temsirolimus inferior to sorafenib in terms of OS in INTORSECT, 2014 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ARCC (Hudes) temsirolimus alone, 2007 | temsirolimus vs interferon alpha | OS 0.73 [0.58; 0.92] | | | | INTORSECT, 2014 | temsirolimus vs sorafenib | | OS 1.31 [1.05; 1.63] | PFS 0.87 [0.71; 1.07] |
| Trial | Treatments | Patients | Method |
|---|
| ARCC (Hudes) temsirolimus alone, 2007 | 25 mg of intravenoustemsirolimus weekly (n=209) vs. 3 million U of interferon alfa (with an increase to 18 millionU) subcutaneously three times weekly (n=207) 3 arms: Temsirolimus alone, Temsirolimus plus interferon and interferon alone | patients with previously untreated, poor-prognosis metastatic renal-cell carcinoma | Sample size: 209/207 Primary endpoint: OS FU duration: | | INTORSECT, 2014 | temsirolimus 25 mg once weekly by intravenous (IV) infusion (n=259) vs. sorafenib 400 mg PO twice daily (n=253) | Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib | Sample size: 259/253 Primary endpoint: PFS FU duration: |
|
| mTOR inhibitor | temsirolimus | versus endocrine therapy alone No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HORIZON, 2013 | temsirolimus + letrozole vs letrozole alone | | | OS 0.89 [0.65; 1.22] PFS 0.90 [0.76; 1.07] |
| Trial | Treatments | Patients | Method |
|---|
| HORIZON, 2013 | oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks) (n=556) vs. letrozole/placebo (n=556) | first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer | double-blind Parallel groups Sample size: 556/556 Primary endpoint: PFS FU duration: |
|
| nontaxane microtubule dynamics inhibitor | eribulin | versus eribulin superior to treatment of physician in terms of overall survival in EMBRACE (Cortes), 2011 | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Trial 301 (Kaufman), 2015 | eribulin vs capecitabine | | | overall survival 0.88 [0.77; 1.00] median 15.9 mo vs. 14.5 mo PFS 1.08 [0.93; 1.25] median 4.1 mo vs. 4.2 mo | | Vahdat, 2013 | eribulin vs ixabepilone | | | | | EMBRACE (Cortes), 2011 | eribulin vs treatment of physician | overall survival 0.81 [0.66; 0.99] median 13.1 mo vs. 10.6 mo Demonstrated | | PFS 0.87 [0.72; 1.06] |
| Trial | Treatments | Patients | Method |
|---|
| Trial 301 (Kaufman), 2015 | eribulin
mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 [expressed as free
base]) intravenously over 2 to 5 minutes on days 1 and 8
until disease progression, unacceptable toxicity, or
patient/investigator request to discontinue (n=554) vs. capecitabine
1.25 g/m2 orally twice per day on days 1 to 14, both in 21-day cycles (n=548) | patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane | open-label Sample size: 554/548 Primary endpoint: Co-primary OS, PFS FU duration: | | Vahdat, 2013 | eribulin mesylate (1.4 mg/m2, 2–5 min
intravenous on days 1 and 8) (n=52) vs. ixabepilone (40 mg/m2,
3 h intravenous on day 1) on a 21-day cycle (n=52) | patients with metastatic breast cancer | open-label Parallel groups Sample size: 52/52 Primary endpoint: incidence of neuropathy FU duration: phase 2 | | EMBRACE (Cortes), 2011 | eribulin mesilate (1·4 mg/m² administered intravenously during 2–5 min on days 1 and 8 of a 21-day
cycle) (n=508) vs. treatment of physician’s choice (n=254) | patients with metastatic breast cancer who had received between two and fi ve previous chemotherapy
regimens (two or more for advanced disease), including an anthracycline and a taxane, unless contraindicated. | open-label Sample size: 508/254 Primary endpoint: overall survival FU duration: |
|
| Phosphoinositide 3-kinase inhibitor | taselisib | versus endocrine therapy alone No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SANDPIPER, 2018 | taselisib + fulvestrant vs fulvestrant alone | | | |
| Trial | Treatments | Patients | Method |
|---|
| SANDPIPER, 2018 | taselisib (4 mg oral, qd) FULV (500 mg) (n=340) vs. palcebo FULV (500 mg) (n=176) | postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, PIK3CA-mutant, unresectable, locally advanced or metastatic breast cancer after recurrence or progression during or after an aromatase inhibitor (AI) therapy | double-blind Sample size: 340/176 Primary endpoint: Progression-free survival (investigator) FU duration: |
|
| poly ADP-ribose polymerase (PARP) inhibitor | olaparib | versus olaparib superior to Physician s choice chemotherapy in terms of PFS in OlympiAD, 2017 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| OlympiAD, 2017 | olaparib vs Physician s choice chemotherapy | PFS 0.58 [0.43; 0.79] Demonstrated | | OS 0.90 [0.63; 1.29] |
| Trial | Treatments | Patients | Method |
|---|
| OlympiAD, 2017 | Olaparib (Olaparib tablet 300mg bd po) (n=205) vs. Physician's choice chemotherapy (Capecitabine 2500 mg/m2 d1-14 q 21, or Vinorelbine 30 mg/m2 d1,8 q 21, or Eribulin 1.4 mg/m2 d1,8 q 21) (n=97) | women with human epidermal growth factor 2 (HER2)–negative metastatic breast cancer with a germline BRCA mutation | open label Sample size: 205/97 Primary endpoint: Progression Free Survival FU duration: 14.5 months |
|
| Selective estrogen receptor downregulators (SERDs) | fulvestrant | versus No demonstrated result for efficacy | 18 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| EFECT (Chia) | fulvestrant 250mg vs exemestane | | | time to progression (TTP) 0.96 [0.82; 1.13] | | D6997L00021 | fulvestrant 500mg vs fulvestrant 250mg | | | | | CONFIRM (Di Leo), 2010 | fulvestrant 500mg vs fulvestrant 250mg | | | | | Xu et al., 2011 | fulvestrant 250mg vs anastrozole | | | | | 0021 (Osborne), 2002 | fulvestrant 250mg vs anastrozole | | | time to progression (TTP) 0.92 [0.74; 1.14] | | 9238IL/0025 | fulvestrant 250mg vs tamoxifen | | | | | GEICAM/2006-10 | fulvestrant + anastrozole vs anastrozole | | | | | 9238UK/0005 (combination) | fulvestrant + anastrozole vs exemestane | | | | | 0020 (Howell), 2002 | fulvestrant 250mg vs anastrozole | | | time to progression (TTP) 0.98 [0.79; 1.21] | | FINDER 1 (Ohno), 2010 | fulvestrant 500mg vs fulvestrant 250mg | | | | | FINDER 2, 2010 | fulvestrant 500mg vs fulvestrant 250mg | | | | | 0025 (Howell), 2004 | fulvestrant 250mg vs tamoxifen | | | time to progression (TTP) 1.18 [0.97; 1.44] | | FIRST (Robertson), 2010 | fulvestrant 500mg vs anastrozole | time to progression (TTP) 0.66 [0.47; 0.92] | | | | SoFEa (Johnston) combination, 2012 | fulvestrant + anastrozole vs exemestane | | | PFS 0.95 [0.79; 1.14] time to progression (TTP) 0.95 [0.79; 1.14] | | FACT (Bergh), 2012 | fulvestrant + anastrozole vs anastrozole | | | OS 1.00 [0.76; 1.32] PFS 0.99 [0.81; 1.20] RR 0.92 [0.54; 1.57] time to progression (TTP) 0.99 [0.82; 1.20] | | Mehta(SWOG-S0226), 2012 | fulvestrant + anastrozole vs anastrozole | PFS 0.80 [0.68; 0.94] time to progression (TTP) 0.80 [0.68; 0.94] | | OS 0.81 [0.65; 1.00] RR 1.33 [0.83; 2.14] | | 9238UK/0005 (fluvestrant alone) | fluvestrant 250mg vs exemestane | | | | | SoFEa (Johnston) fluvestrant alone, 2012 | fluvestrant 250mg vs exemestane | | | |
| Trial | Treatments | Patients | Method |
|---|
| EFECT (Chia) | Fulvestrant 500 mg (2 x 5 mL, im injections) administered as a loading dose on Day 0,
followed by 250 mg (1 x 5 mL) on Day 14, Day 28 and monthly (ie, 28 ± 3 days) thereafter. (n=-9) vs. Exemestane 25 mg administered once daily by mouth (po) from Day 0. (n=-9) | hormone receptor positive postmenopausal women with advanced breast cancer | double-blind Sample size: -9/-9 Primary endpoint: Time to disease progression FU duration: | | D6997L00021 | Fulvestrant 500mg (2 syringes of Fulvestrant 250mg), Fulvestrant 500 mg i.m. every 28 (+/- 3) days plus an additional 500 mg on day 14 (+/-3) of first month only (n=-9) vs. Fulvestrant 250mg (1 syringe of fulvestrant 250mg + 1 syringe matching placebo), Fulvestrant 250 mg and matching placebo i.m. every 28 (+/- 3) days plus an additional 2 placebo syringes on day 14 (+/-3) of first month only (n=-9) | Chinese postmenopausal women with oestrogen receptor positive advanced breast cancer who have failed a prior endocrine treatment | double-blind Sample size: -9/-9 Primary endpoint: FU duration: | | CONFIRM (Di Leo), 2010 | fulvestrant 500 mg
(500 mg intramuscularly [IM] on day 0, then 500 mg IM on days 14 and 28 and every 28 days
thereafter) (n=-9) vs. fulvestrant 250 mg every 28 days (n=-9) | women with oestrogen receptor positive advanced breast cancer who have failed on a previous endocrine treatment | double-blind Sample size: -9/-9 Primary endpoint: Time to Progression FU duration: | | Xu et al., 2011 | fulvestrant 250 mg/month (n=121) vs. 1 mg/day anastrozole (n=113) | receptor positive postmenopausal advanced breast cancer. | double-blind Sample size: 121/113 Primary endpoint: Time to Disease Progression FU duration: | | 0021 (Osborne), 2002 | intramuscular injection of fulvestrant 250 mg once monthly (n=-9) vs. daily oral dose of anastrozole 1 mg (n=-9) | postmenopausal women with advanced breast cancer | double-blind Sample size: -9/-9 Primary endpoint: time to tumor progression FU duration: | | 9238IL/0025 | intramuscular injection 250 mg (n=-9) vs. (n=-9) | first-line treatment for postmenopausal women with advanced breast cancer. | double-blind Sample size: -9/-9 Primary endpoint: Time to disease progression FU duration: | | GEICAM/2006-10 | 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral anastrozol per day during 5 years (n=-9) vs. Anastrozol 1 mg daily for 5 yeras (n=-9) | Postmenopausal women with hormone receptor positive and negative Her2 tumours | open label Sample size: -9/-9 Primary endpoint: free disease survival FU duration: | | 9238UK/0005 (combination) | (n=-9) vs. (n=-9) 3 arms: fulvestrant and anastrozole, fulvestrant and placebo, and exemestane alone | postmenopausal locally advanced / metastatic breast cancer patients who have progressed on NSAIs | double-blind Sample size: -9/-9 Primary endpoint: Progression-free survival FU duration: | | 0020 (Howell), 2002 | fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection (n=-9) vs. oral dose of anastrozole 1 mg (n=-9) | | open-label Sample size: -9/-9 Primary endpoint: time to progression FU duration: | | FINDER 1 (Ohno), 2010 | 28-day cycles of fulvestrant (n=-9) vs. (n=-9) | postmenopausal Japanese women with advanced breast cancer | Sample size: -9/-9 Primary endpoint: objective response rate (ORR) FU duration: | | FINDER 2, 2010 | 500 mg (high dose [HD]; 500 mg/month plus 500 mg on day 14 of Month 1). (n=-9) vs. fulvestrant: 250 mg/month (approved dose [AD]); (n=-9) | Western postmenopausal women recurring or progressing after prior endocrine therapy | Sample size: -9/-9 Primary endpoint: objective response rate (ORR) FU duration: | | 0025 (Howell), 2004 | fulvestrant 250 mg, via intramuscular injection, once monthly; (n=313) vs. tamoxifen 20 mg, orally, once daily (n=274) | advanced breast cancer in postmenopausal women previously untreated with endocrine therapy | double-blind Sample size: 313/274 Primary endpoint: FU duration: | | FIRST (Robertson), 2010 | 500 mg intramuscular injection (n=-9) vs. anastrozole
1 mg oral tablet (n=-9) | First Line Hormonal Treatment for Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | SoFEa (Johnston) combination, 2012 | Fulvestrant With Concomitant Anastrozole (n=-9) vs. Exemestane (n=-9) 3 arms: fulvestrant and anastrozole, fulvestrant and placebo, exemestane alone | Postmenopausal Women With ER+ve Locally Advanced/Metastatic Breast Cancer Following Progression on Non-Steroidal Aromatase Inhibitors | Sample size: -9/-9 Primary endpoint: FU duration: | | FACT (Bergh), 2012 | fulvestrant 500 mg intramuscular on
day 1 and 250mgon days 15 and 29 and thereafter every fourth week3 days,
until proven progression or undue toxicity, in combination with anastrozole
1 mg orally per day (n=258) vs. anastrozole orally at 1 mg
per day until proven progression or undue toxicity
(n=256)
| first-line therapy for patients with receptor-positive postmenopausal breast cancer
| opan-label Sample size: 258/256 Primary endpoint: Time to Progression FU duration:
| | Mehta(SWOG-S0226), 2012 | Fulvestrant
was administered intramuscularly at a dose of 500 mg on day 1 and 250 mg
on days 14 and 28 and monthly thereafter. (n=-9) vs. 1 mg of anastrozole orally every day
(group 1), with crossover to fulvestrant alone strongly encouraged if the disease
progressed, (n=-9) | Postmenopausal women with previously untreated with hormone-receptor (HR)-positive | Sample size: -9/-9 Primary endpoint: FU duration: | | 9238UK/0005 (fluvestrant alone) | fulvestrant Intramuscular injection on days 1, 15, and 29 and then once monthly until disease progression
(n=-9) vs. exemestane oral, once daily until disease progression.
(n=-9) 3 arms: fulvestrant and anastrozole, fulvestrant and placebo, and exemestane alone
| postmenopausal locally advanced / metastatic breast cancer patients who have progressed on NSAIs
| double-blind Sample size: -9/-9 Primary endpoint: Progression-free survival FU duration:
| | SoFEa (Johnston) fluvestrant alone, 2012 | fulvestrant intramuscularly (IM) on days 1, 15, and 29 and then once monthly (n=-9) vs. exemestane once daily (n=-9) 3 arms: fulvestrant and anastrozole, fulvestrant and placebo, exemestane alone
| Postmenopausal Women With ER+ve Locally Advanced/Metastatic Breast Cancer Following Progression on Non-Steroidal Aromatase Inhibitors
| Parallel groups Sample size: -9/-9 Primary endpoint: FU duration:
|
|
| selective estrogen receptor modulator (SERM) osteoporosis | tamoxifen | versus No demonstrated result for efficacy | 22 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Beelen, 2014 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Beex, 2006 | (n=-9) vs. (n=-9) | first line endocrine treatment in advanced breast | Sample size: -9/-9 Primary endpoint: FU duration: | | Sawka, 1997 | (n=-9) vs. (n=-9) | metastatic breast cancer in premenopausal women | Sample size: -9/-9 Primary endpoint: FU duration: | | Kuss, 1997 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Stuart, 1996 | (n=-9) vs. (n=-9) | advanced and recurrent breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | Willsher, 1996 | (n=-9) vs. (n=-9) | Locally advanced breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | Muss, 1994 | (n=-9) vs. (n=-9) | patients with metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | Gill, 1993 | (n=-9) vs. (n=-9) | patients with metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | Castiglione-Gertsch, 1993 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Spooner, 1991 | (n=-9) vs. (n=-9) | advanced breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | De Lena, 1990 | (n=-9) vs. (n=-9) | advanced breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | Takatsuka, 1989 | (n=-9) vs. (n=-9) | advanced breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | Kellokumpu-Lehtinen, 1987 | (n=-9) vs. (n=-9) | advanced breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | Ettinger, 1986 | (n=-9) vs. (n=-9) | advanced breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | Gockerman, 1986 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Buchanan, 1986 | (n=-9) vs. (n=-9) | premenopausal patients with advanced breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | van, 1986 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Ingle, 1986 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Mauriac, 1986 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Viladiu, 1985 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Mouridsen, 1985 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Perry, 1985 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| selective estrogen receptor modulator (SERM) osteoporosis | toremifene | versus No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Nomura, 1993 | (n=-9) vs. (n=-9) | patients with advanced or recurrent breast cancer | double-blind Sample size: -9/-9 Primary endpoint: FU duration: | | Gershanovich, 1997 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Milla-Santos, 2001 | toremifene (TOR) 60 mgs/dayly/o.r. (n=-9) vs. tamoxifen (TAM) 40 mgs/dayly/o.r. (n=-9) | postmenopausal women with advanced breast cancer, without previous systemic therapy | double-blind Sample size: -9/-9 Primary endpoint: FU duration: | | Hayes, 1995 | toremifene (TOR; 60 mg/d [TOR60] and 200 mg/d (n=-9) vs. tamoxifen (TAM; 20 mg/d) (n=215) | postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer | Sample size: -9/215 Primary endpoint: FU duration: | | Stenbygaard, 1993 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Pyrhonen, 1997 | (n=-9) vs. (n=-9) | post-menopausal patients with advanced breast cancer who have not had prior systemic therapy | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| Taxanes | docetaxel | versus combination chemotherapy No demonstrated result for efficacy | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| 304 Study Group, 1999 | docetaxel 100 mg/m2 intravenously (i.v.) every 3 weeks (n=203) vs. mitomycin 12 mg/m2 i.v. every 6 weeks plus vinblastine 6 mg/m2 i.v. every 3 weeks (n=189) | patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy | open-label Sample size: 203/189 Primary endpoint: FU duration: | | Sjostrom, 1999 | Docetaxel at a dose of 100 mg/m2 every 3 weeks (n=143) vs. sequential methotrexate and 5-fluorouracil (n=139) | patients with advanced breast cancer who had failed previous anthracycline treatment | Sample size: 143/139 Primary endpoint: FU duration: | | TXT Group, 2002 | docetaxel (100 mg m(-2)) every 3 weeks (n=-9) vs. 5-fluorouracil+vinorelbine: 5-fluorouracil (750 mg m(-2) per day continuous infusion) D1-5 plus vinorelbine (25 mg m(-2)) D1 and D5 of each 3-week cycle (n=-9) | patients with metastatic breast cancer after failure of neo/adjuvant or one line of palliative anthracycline-based chemotherapy | Sample size: -9/-9 Primary endpoint: FU duration: | | Bontenbal, 2005 | AT (doxorubicin 50 mg/m(2) and docetaxel 75 mg/m2) (n=-9) vs. FAC (fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2); (n=-9) | first-line chemotherapy in patients with metastatic breast cancer: | Sample size: -9/-9 Primary endpoint: FU duration: | | Blohmer, 2010 | ED (epirubicin 75 mg/m(2) and docetaxel 75 mg/m(2)) (n=-9) vs. EC (epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2)). (n=-9) | first-line therapy for women with metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | Bonneterre, 2004 | docetaxel 75 mg m(-2) plus epirubicin 75 mg m(-2) (n=-9) vs. 5-fluorouracil 500 mg m(-2) plus epirubicin 75 mg m(-2) and cyclophosphamide 500 mg m(-2) intravenously once every 3 weeks for up to eight cycles (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | HERNATA, 2011 | docetaxel 100 mg/m(2) day 1 (n=-9) vs. vinorelbine 30 to 35 mg/m(2) on days 1 and 8 (n=-9) | first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | JCOG, 2005 | (n=-9) vs. (n=-9) | first-line chemotherapy in metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| Taxanes | docetaxel | versus Every three weeks regimen No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Rivera , 2008 | Weekly Docetaxel vs Every three weeks Docetaxel | | | | | Tabernero , 2004 | Weekly Docetaxel vs Every three weeks Docetaxel | | | | | Sedky , 2002 | Weekly Docetaxel vs Every three weeks Docetaxel | | | | | Willemse , 2007 | Weekly Docetaxel vs Every three weeks Docetaxel | | | |
| Trial | Treatments | Patients | Method |
|---|
| Rivera , 2008 | Weekly Docetaxel 35–40 mg/m2 (n=-9) vs. Every three weeks Docetaxel 75–100 mg/m2 (n=-9) | Metastatic patients with metastatic breast cancer | open Sample size: -9/-9 Primary endpoint: FU duration: | | Tabernero , 2004 | Weekly Docetaxel 40 mg/m2 (n=-9) vs. Every three weeks Docetaxel 100 mg/m2 (n=-9) | Metastatic | Sample size: -9/-9 Primary endpoint: FU duration: | | Sedky , 2002 | Weekly Docetaxel 35 mg/m2 (n=-9) vs. Every three weeks Docetaxel 100 mg/m2 (n=-9) | Metastatic | Sample size: -9/-9 Primary endpoint: FU duration: | | Willemse , 2007 | Weekly Docetaxel 36 mg/m2 (n=-9) vs. Every three weeks Docetaxel 100 mg/m2 (n=-9) | Metastatic | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| Taxanes | nab-paclitaxel | versus single-agent chemotherapy No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Gradishar, 2009 | weekly and every 3 week (q3w) nab-paclitaxel (n=302) vs. docetaxel (n=0) | first-line treatment in patients with MBC | Sample size: 302/0 Primary endpoint: FU duration: | | Roy, 2008 | weekly nab (nanoparticle albumin-bound)-paclitaxel in combination with gemcitabine (n=50) vs. (n=0) | patients with previously untreated metastatic breast cancer | Sample size: 50/0 Primary endpoint: FU duration: |
|
| Taxanes | paclitaxel | versus combination chemotherapy No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Jassem, 2001 | (n=-9) vs. (n=-9) | first-line therapy for women with metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | ANZ TITG, 1999 | paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) (n=-9) vs. standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin re (n=-9) | front-line therapy in untreated metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | TOG, 2005 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | CECOG BM1, 2005 | gemcitabine (1,000 mg/m(2), days 1 and 4), epirubicin (90 mg/m(2), day 1), and paclitaxel (175 mg/m(2), day 1) (n=-9) vs. FU (500 mg/m(2), day 1), epirubicin (90 mg/m(2), day 1), and cyclophosphamide (500 mg/m(2), day 1) (n=-9) | first-line chemotherapy in metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | UKCCCR AB01, 1997 | EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2) (n=-9) vs. EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles (n=-9) | first-line chemotherapy for metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| Taxanes | paclitaxel | versus Every three weeks regimen No demonstrated result for efficacy Weekly Paclitaxel inferior to Every three weeks Paclitaxel in terms of overall response in Frasci , 2005 Weekly Paclitaxel inferior to Every three weeks Paclitaxel in terms of progression free survival in Sikov , 2002 | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CLGB 9840 (Seidman), 2008 | Weekly Paclitaxel vs Every three weeks Paclitaxel | overall survival 0.78 [0.65; 0.94] progression free survival 0.74 [0.63; 0.86] | | overall response 1.19 [0.96; 1.48] | | Gradishar , 2009 | Weekly Paclitaxel vs Every three weeks Docetaxel | | | overall response 1.27 [0.90; 1.79] | | Fountzilas , 2008 | Weekly Paclitaxel vs Every three weeks Docetaxel | | | overall response 1.29 [0.98; 1.69] overall survival 0.72 [0.50; 1.04] progression free survival 1.04 [0.78; 1.39] | | Frasci , 2006 | Weekly Paclitaxel vs Every three weeks Paclitaxel | | | overall response 1.13 [0.99; 1.28] overall survival 0.60 [0.34; 1.05] progression free survival 0.99 [0.62; 1.59] | | Frasci , 2005 | Weekly Paclitaxel vs Every three weeks Paclitaxel | | overall response 1.61 [1.18; 2.19] | overall survival 0.79 [0.46; 1.34] progression free survival 1.09 [0.73; 1.63] | | Sikov , 2002 | Weekly Paclitaxel vs Every three weeks Paclitaxel | | progression free survival 1.67 [1.05; 2.65] | overall response 0.99 [0.72; 1.36] overall survival 0.98 [0.62; 1.55] | | Khoo , 2006 | split dose vs Every three weeks Paclitaxel | | | overall response 1.07 [0.77; 1.49] progression free survival 1.04 [0.70; 1.54] |
| Trial | Treatments | Patients | Method |
|---|
| CLGB 9840 (Seidman), 2008 | Weekly Paclitaxel 80 mg/m2 (n=-9) vs. Every three weeks Paclitaxel 175 mg/m2 (n=-9) | Metastatic | Sample size: -9/-9 Primary endpoint: FU duration: | | Gradishar , 2009 | Weekly Nab-paclitaxel 100 mg/m2 (n=-9) vs. Every three weeks Docetaxel 100 mg/m2 (n=-9) | Metastatic | Sample size: -9/-9 Primary endpoint: FU duration: | | Fountzilas , 2008 | Weekly Paclitaxel 80 mg/m2 (n=-9) vs. Every three weeks Gemc. Docetaxel 75 mg/m2 (n=-9) | Metastatic | Sample size: -9/-9 Primary endpoint: overall survival FU duration: | | Frasci , 2006 | Weekly Epi CDDP Paclitaxel 120 mg/m2 (n=-9) vs. Every three weeks Epi Paclitaxel 175 mg/m2 (n=-9) | LABC | Sample size: -9/-9 Primary endpoint: FU duration: | | Frasci , 2005 | Weekly Epi CDDP Paclitaxel 120 mg/m2 (n=-9) vs. Every three weeks Epi Paclitaxel 175 mg/m2 (n=-9) | Metastatic | Sample size: -9/-9 Primary endpoint: FU duration: | | Sikov , 2002 | Weekly Paclitaxel 150 mg/m2 (n=-9) vs. Split D1,8 every three weeks Paclitaxel 175 mg/m2 (n=-9) | Metastatic | Sample size: -9/-9 Primary endpoint: FU duration: | | Khoo , 2006 | split-dose paclitaxel or docetaxel in combination with gemcitabine (n=-9) vs. Every three weeks Gemc. Paclitaxel 175 mg/m2 (n=-9) | Metastatic patients with metastatic breast cancer (MBC) who had previously received anthracyclines | Sample size: -9/-9 Primary endpoint: FU duration: |
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| Taxanes | paclitaxel | versus single-agent chemotherapy No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Dieras, 1995 | paclitaxel 175 mg/m2 given as a 3-hour infusion every 3 weeks (n=-9) vs. mitomycin 12 mg/m2 given as an intravenous infusion every 6 weeks (n=-9) | advanced breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | ECOG E1193 (B), 2003 | paclitaxel (175 mg/m(2)/24 h), (n=-9) vs. doxorubicin (60 mg/m(2)), (n=-9) | patients with metastatic breast cancer | Sample size: -9/-9 Primary endpoint: FU duration: | | EORTC 10923, 2000 | (n=-9) vs. (n=-9) | first-line therapy of advanced breast cancer | Sample size: -9/-9 Primary endpoint: progression-free survival FU duration: | | Talbot, 2002 | i.v. paclitaxel (175 mg m(-2), (n=-9) vs. 3-week cycles of intermittent oral capecitabine (1255 mg m(-2) twice daily, days 1-14, (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
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