Drug, U.S. FDA-Labeled Approval(s) | Study Name | Phase | Study Population, Size | Intervention(s) | Primary Outcome(s) | Selected Secondary Outcomes | Reference(s) |
---|---|---|---|---|---|---|---|
Alemtuzumab | |||||||
B-CLL, previously untreated | 3 | N = 297 | Alemtuzumab versus chlorambucil | PFS: 14.6 versus 11.7 months* | RR: 83.2% versus 55.4% * | (Hillmen et al., 2007) | |
Initial accelerated approval | |||||||
N/A | N = 149; 3 single-arm studies | Alemtuzumab | PR: 21%–31% | PI | |||
CR: 0%–2% | |||||||
Axitinib | |||||||
Advanced RCC after failure of prior systemic therapy | AXIS | 3 | N = 723 | Axitinib versus sorafenib | PFS: 6.7 versus 4.7 months* | ORR: 19.4% versus 9.4%* | (Rini et al., 2011) |
Bevacizumab | |||||||
Metastatic CRC, with 5-FU, first- or second-line therapy | Study 2107 | 3 | Previously untreated, N = 813 | Bevacizumab versus placebo, with IFL | OS: 20.3 versus 15.6 months* | PFS: 10.6 versus 6.2 months* | (Hurwitz et al., 2004) |
ORR: 44.8% versus 34.8%* | |||||||
E3200 | 3 | Previously treated, N = 829 | FOLFOX4, bevacizumab, versus both | OS: 12.9 (combination) versus 10.8 months (FOLFOX)* | PFS: 7.3 versus 4.7 months* | (Giantonio et al., 2007) | |
ORR: 22.7% versus 8.6% * | |||||||
2 | Previously treated, N = 339 | Bevacizumab with 5-FU/LV | ORR 1% | PFS: 3.5 months | (Chen et al., 2006) | ||
OS: 9 months | |||||||
Metastatic CRC, second-line after first progression on bevacizumab-based chemotherapy | ML18147 | 3 | N = 820 | Bevacizumab with chemotherapy (oxaliplatin- or irinotecan-based) versus chemotherapy alone | OS: 11.2 versus 9.8 months* | PFS: 5.7 versus 4.1 months* | (Bennouna et al., 2013) |
Advanced NSCLC, nonsquamous, with carboplatin/paclitaxel, first-line | E4599 | 3 | N = 878 | Paclitaxel and carboplatin +/− bevacizumab | OS: 12.3 versus 10.3 months* | PFS: 6.2 versus 4.5 months* | (Sandler et al., 2006) |
ORR: 33% versus 15%* | |||||||
AVAiL | 3 | N = 1043 | Cisplatin/gemcitabine with bevacizumab 7.5 mg/kg versus bevacizumab 15 mg/kg versus placebo | PFS: 6.7 (7.5 mg/kg) versus 6.5 (15 mg/kg) versus 6.1 months (chemotherapy) * | OS: 13.1 (placebo) versus 13.6 months (7.5 mg/kg) versus 13.4 months (15 mg/kg) | (Reck et al., 2009, 2010) | |
Glioblastoma, progressive after prior therapy | NCI-06-C-0064E | 2 | N = 48 | Bevacizumab | Radiographic response rate: 71% | OS: 31 weeks | (Kreisl et al., 2009) |
Accelerated approval | PFS: 16 weeks | ||||||
BRAIN | 2 | First or second relapse, N = 167 | Bevacizumab +/− irinotecan | PFS at 6 months: 42.6% bevacizumab versus 50.3% combination* | OS: 9.2 versus 8.7 months (significance testing not provided) | (Friedman et al., 2009) | |
Ovarian cancer, advanced newly diagnosed and stage IV | 3 | N = 1873 | Carboplatin + paclitexal with placebo or bevacizumab initiation or bevacizumab throughout | PFS 10.3 versus 11.2 versus 14.1 months | OS 39.3 versus 38.7 versus 39.7 | (Burger et al., 2011) | |
Metastatic RCC, with INFα | AVOREN Trial | 3 | Previously untreated, N = 649 | IFN-α2a with bevacizumab versus IFN with placebo | OS: 23.3 versus 21.3 months | PFS: 10.2 versus 5.4 months* | (Escudier et al., 2007a, 2010) |
Bortezomib | |||||||
Multiple myeloma, first-line | VISTA | 3 | Ineligible for stem cell transplant, N = 682 | Melphalan/prednisone +/− bortezomib | TTP: 24 versus 16.6 months* | CR: 30% versus 4%* | (San Miguel et al., 2008) |
OS, median: 56.4 versus 43.1 months * | |||||||
Multiple myeloma, relapsed/refractory | APEX | 3 | Relapsed after 1-3 prior therapies, N = 669 | Bortezomib versus high-dose dexamethasone | TTP: 6.22 versus 3.49 months* | ORR: 38% versus 18%* | (Richardson et al., 2005, 2007) |
OS: 29.8 versus 23 months* | |||||||
SUMMIT | 2 | N = 202 | Bortezomib (+dexamethasone if poor response) | ORR: 35% | OS: 16 months | (Richardson et al., 2003) | |
DR: 12 months | |||||||
CREST | 2 | N = 54 | Bortezomib (two dosages, with dexamethasone if poor response) | ORR: 50% (1.3 mg/m2), 33% (1 mg/m2) | TTP: 11 months (1.3 mg/m2), 7 months (1 mg/m2) | (Jagannath et al., 2004) | |
OS: median not reached (1.3 mg/m2) and 26.7 months (1 mg/m2) | |||||||
Multiple myeloma, SQ administration | 3 | Relapsed after 1–3 prior therapies, N = 222 | Bortezomib SQ versus i.v. | ORR at 4 months: 42% in both groups | TTP: 10.4 versus 11.7 months | (Moreau et al., 2011) | |
OS, 1 year: 72.6% versus 76.7% | |||||||
Mantle cell lymphoma, previously treated | PINNACLE | 2 | N = 155 | Bortezomib | TTP versus historical controls: insufficient controls | ORR: 33% | (Fisher et al., 2006) |
DR 9.2 months | |||||||
TTP: 6.2 months | |||||||
Brentuximab vedotin | |||||||
Hodgkin’s lymphoma, relapsed/refractory after auto SCT or at least two chemotherapy regimens | 2 | N = 102 | Brentuximab vedotin | ORR: 75% | PFS: 5.6 months | (Younes et al., 2012) | |
Accelerated approval | CR 34% | OS: 22.4 months | |||||
sALCL, after failed systemic therapy | 2 | N = 58 | Brentuximab vedotin | ORR: 86% | DR: 12.6 months | PI | |
Accelerated approval | |||||||
Carfilzomib | |||||||
Multiple myeloma, relapsed/refractory | 2 | N = 266 | Carfilzomib | ORR: 23.7% | DR: 7.8 months | (Siegel et al., 2012) | |
Accelerated approval | OS: 15.6 months | ||||||
PFS: 3.7 months | |||||||
Cetuximab | |||||||
Metastatic CRC, K-RAS WT, EGFR+, with FOLFIRI, first-line | CRYSTAL | 3 | N = 1198 | FOLFIRI with versus without cetuximab | PFS: 8.9 versus 8.0 months* | OS (K-RAS WT): 23.5 versus 20 months* | (Van Cutsem et al., 2009, 2011) |
PFS (K-RAS WT): 9.9 versus 8.4 months* | ORR (K-RAS WT): 59.3 versus 43.2%* | ||||||
Metastatic CRC, K-RAS WT, EGFR+, with irinotecan, in patients refractory to irinotecan-based chemotherapy | BOND | 2 | N = 329 | Cetuximab with versus without irinotecan | ORR: 22.9% (combination) versus 10.8% (cetuximab)* | TTP: 4.1 versus 1.5 months* | (Cunningham et al., 2004) |
OS: 8.6 versus 6.9 months | |||||||
Metastatic CRC, K-RAS WT, EGFR+, single agent, in patients who have failed oxaliplatin and irinotecan-based therapy or are intolerant to irinotecan | N = 572 | Cetuximab versus BSC | OS:6.1 months versus 4.6 months* | PFS: HR 0.68* | (Jonker et al., 2007) | ||
Locoregionally advanced SCCHN, with radiation therapy | 3 | N = 424 | Radiotherapy with versus without cetuximab | Duration of disease control: 24.4 versus 14.9 months* | OS: 49 versus 29.3 months* | (Bonner et al., 2006) | |
PFS: 17.1 versus 12.4 months* | |||||||
Recurrent or metastatic SCCHN, with platinum-based therapy/5-FU | EXTREME | 3 | N = 442 | Platinum-based chemotherapy with versus without cetuximab | OS: 10.1 versus 7.4 months* | PFS: 5.6 versus 3.3 months* | (Vermorken et al., 2008) |
ORR: 36% versus 20%* | |||||||
Recurrent locoregional/metastatic SCCHN, single agent, after failure of platinum-based chemotherapy | 2 | N = 103 | Cetuximab, with platinum-based chemotherapy if poor response | ORR: 13% | TTP: 70 days | (Vermorken et al., 2007) | |
OS: 178 days | |||||||
Crizotinib | |||||||
NSCLC, locally advanced or metastatic, ALK positive | Study A | 2 | N = 136 | Crizotinib | ORR: 50% | DR: 41.9 weeks | PIa |
Accelerated approval | |||||||
Study B | 1 | N = 119 | Crizotinib | ORR: 61% | DR: 48 weeks | b | |
PFS: 10 months | |||||||
Dasatinib | |||||||
CML-CP, Ph+, newly diagnosed | DASISION | 3 | CML-CP, N = 519 | Dasatinib (once daily) versus imatinib | CCyR at 12 months: 77 versus 66%* | MMR: 52% versus 34%* | (Kantarjian et al., 2010, 2012) |
Accelerated approval | |||||||
CML-CP, resistant or intolerant to imatinib, once daily dosing | 3 | CML-CP, N = 670 | Dasatinib dose optimization | MCyR: | OS, estimated at 24 months | (Shah et al., 2008, 2010) | |
Accelerated approval for daily dosing | 140 mg daily: 63% | 140 mg daily: 94$ | |||||
70 mg BID: 61% | 70 mg BID: 88% | ||||||
100 mg daily: 63% | 100 mg daily: 91% | ||||||
50 mg BID: 61% | 50 mg BID: 90% | ||||||
START-C | 2 | CML-CP, N = 186 | Dasatinib BID | MCyR: 52% | CHR: 90% | (Hochhaus et al., 2007) | |
START-R | 2 | CML-CP, N = 150 | Dasatinib BID (70 mg PO BID) versus imatinib | MCyR at 24 months: 53% versus 33%* | CHR: 93% versus 82%* | (Kantarjian et al., 2007a) | |
TTF: not reached versus 3.5 months* | |||||||
PFS: HR 0.14* | |||||||
CML advanced phase or Ph+ ALL, resistant or intolerant to imatinib | 3 | CML-AP, MB, LB, Ph+ ALL, N = 611 | Dasatinib 140 mg daily versus 70 mg BID | MaHR: Daily versus BID | OS: 63 vs. 72% (no significant difference) | (Kantarjian et al., 2009; Lilly et al., 2010; Saglio et al., 2010a) | |
Accelerated approval | CML-AP: 66% versus 68% | CML-AP: 63% versus 72%, Est 24-month | |||||
CML-MB: 28% versus 28% | CML-MB: 7.9 versus 7.7 months, median | ||||||
CML-LB: 42% versus 32% | CML-LB: 11.4 versus 9.0 months, median | ||||||
Ph+ ALL: 38% vs32% | Ph+ ALL: 6.5 versus 9.1 months, median | ||||||
START-A | 2 | CML-AP, N = 174 | Dasatinib BID | MaHR: 64% | PFS, at 12 months: 66% | (Apperley et al., 2009) | |
OS, at 12 months: 82% | |||||||
START-B and START-L | 2 | CML-MB, N = 74 | Dasatinib BID | MaHR: 34% (CML-MB), 31% (CML-LB) | PFS: 6.7 months (CML-MB), 3.0 months (CML-LB) | (Cortes et al., 2007) | |
CML-LB, N = 42 | OHR: 53% (CML-MB), 36% (CML-LB) | OS: 11.8 months (CML-MB), 5.3 months (CML-LB) | |||||
START-L | 2 | Ph+ ALL, N = 36 | Dasatinib BID | MaHR: 42% | PFS: 3 months | (Ottmann et al., 2007) | |
OHR: 50% | OS at 24 months: 31% | ||||||
Denileukin diftitox | |||||||
Persistent or recurrent CD25+ CTCL | 3 | CTCL, stage IA to III, N = 144 | Denileukin diftitox versus placebo | ORR: 49.1% (18 μg/kg)* versus 37.8% (9 μg/kg)* versus 15.9% (placebo) | PFS: 971 days (18 μg/kg) * versus 794 days (9 μg/kg) * versus 124 days (placebo) | (Prince et al., 2010) | |
Initial accelerated approval | |||||||
3 | CTCL, stage Ib to IVa, N = 71 | Denileukin diftitox | ORR: 30% | DR: 6.9 months | (Olsen et al., 2001) | ||
Erlotinib | |||||||
Locally advanced or metastatic NSCLC, maintenance after first-line therapy | SATURN | 3 | N = 889 | Erlotinib versus placebo | PFS: 12.3 versus 11.1 weeks* | OS: 12.0 vs11.0 months* | (Cappuzzo et al., 2010; Shepherd et al., 2005). |
Locally advanced or metastatic NSCLC, after prior failed chemotherapy | 3 | N = 731 | Erlotinib | OS: 6.7 versus 4.7 months* | ORR: 8.9% versus <1%* | ||
PFS: 2.2 versus 1.8 months* | |||||||
Locally advanced or metastatic pancreatic cancer, with gemcitabine, first-line | 3 | N = 569 | Gemcitabine with versus without erlotinib | OS: 6.24 versus 5.91 months* | One year survival: 23% versus 17%* | (Moore et al., 2007) | |
PFS: 3.75 versus 3.55 months* | |||||||
Everolimus | |||||||
Advanced HER2(−), HR(+) breast cancer, postmenopausal women, with exemestane, after failed letrozole or anastrozole | BOLERO-2 | 3 | N = 724 | Exemestane, with everolimus versus placebo | PFS: 10.6 versus 4.1 months* | ORR: 9.5% versus 0.4%* | (Baselga et al., 2012a) |
Progressive PNET, locally advanced/metastatic disease | RADIANT-3 | 3 | N = 410 | Everolimus versus placebo | PFS:11.0 versus 4.6 months* | (Yao et al., 2011) | |
Advanced RCC, after failure of sunitinib or sorafenib | RECORD-1 | 3 | N = 410 | Everolimus versus placebo | PFS: 4.0 versus 1.9 months* | OS: no significant difference | (Motzer et al., 2008) |
Renal angiomyolipoma with TSC, not requiring immediate surgery | EXIST-2 | 3 | N = 118 | Everolimus versus placebo | ORR: 42% versus 0%* | (Bissler et al., 2013) | |
SEGA, TSC-associated, unresectable | EXIST-1 | 3 | N = 117 | Everolimus (suspension) versus placebo | 50%+ reduction of target lesion volume: 35% versus 0%* | Est PFS at 6 months: 100% versus 86% * | (Franz et al., 2013) |
Accelerated approval for oral suspension and tablets | |||||||
1-2 | N = 28 | Everolimus (tablets) | Median reduction in primary lesion volume at 6 months: 0.80 cm3* | Median one fewer seizure over 6 months* | (Krueger et al., 2010) | ||
Ibritumomab tiuxetan | |||||||
Follicular lymphoma, consolidation therapy after response to first-line therapy | FIT | 3 | Stage III/IV, N = 414 | Ibritumomab regimen versus observation | PFS: 36.5 versus 13.3 months* | CR/CRu: 87.5% versus 53.3% (significance testing not provided) | (Morschhauser et al., 2008) |
Relapsed/refractory low-grade or follicular non–Hodgkin’s lymphoma | 3 | Rituximab naïve, N = 130 | Ibritumomab regimen versus rituximab | ORR: 83% versus 55%* | TTP: 12.1 versus 10.1 months | (Witzig et al., 2002a) | |
Accelerated approval | |||||||
NS | Refractory to rituximab, N = 54 | Ibritumomab regimen | ORR: 74% | TTP: 6.8 months | (Witzig et al., 2002b) | ||
CR: 15% | DR: 6.4 months | ||||||
2 | N = 30 | Ibritumomab regimen | ORR: 83% | TTP: 9.4 months | (Wiseman et al., 2002) | ||
CR 37% | DR: 11.6 months | ||||||
Imatinib | |||||||
Ph+ CML, chronic phase, newly diagnosed | IRIS | 3 | N = 1106 | Imatinib versus INF-α + low-dose cytarabine | PFS at 84 months: 81.2% versus 60.6%* | OS at 84 months: 86.4% versus 83.3%* | (O’Brien et al., 2003) |
Initial accelerated approval | CHR: 96.6% versus 56.6%* | ||||||
MCyR: 85.4% versus 16.8%* | |||||||
Ph+ CML (CP, AP, or BC), after failed IFN-α therapy | 2 | CML, late chronic phase, N = 532 | Imatinib | MCyR: 60% | CHR: 96% | (Hochhaus et al., 2008; Kantarjian et al., 2002) | |
Initial accelerated approval | OS, 6 year estimated: 76% | ||||||
CCyR 57% | |||||||
2 | CML-AP, N = 235 | Imatinib | CHR: 53% | MCyR: 24% | (Talpaz et al., 2002) | ||
PFS, 12 month: 59% | |||||||
OS, 12 month: 74% | |||||||
2 | CML-blast crisis, N = 260 | Imatinib | Sustained hematological response, lasting at least 4 weeks: 30.6% | DR, hematological: 10 months | (Sawyers et al., 2002) | ||
MCyR: 16.2% | |||||||
OS: 6.9 months | |||||||
CML, pediatric (initial) accelerated approval | 2 | Pediatric CML-CP, N = 51 | Imatinib | CHR 78% at 8 weeks | CCyR 65% | PI | |
1 | Pediatric CML-CP, recurrent, N = 14 | Imatinib | CCyR 7/13 | PI | |||
1 | CML-CP, resistant to IFN-α, N = 3 | Imatinib | CCyR: 2 of 3 patients | PI | |||
KIT+ GIST, adjuvant treatment after resection | Scandinavian Sarcoma Group XVIII/AIO | 3 | N = 397 | Imatinib for 12 versus 36 months | 5-year RFS: 65.6% versus 47.9%* | 5-year OS: 92% versus 81.7%* | (Joensuu et al., 2012) |
Initial accelerated approval | |||||||
ACOSOG Z9001 Trial | N = 713 | Imatinib versus placebo | 1-year RFS: 98% versus 83%* | 1-year OS: No significant difference | (Dematteo et al., 2009) | ||
KIT+ GIST, unresectable/metastatic | SWOB S0033 | 3 | N = 746 | Imatinib daily versus BID | PFS: 18 months (daily) versus 20 months (BID) | OS: 55 months (daily) versus 51 months (BID) | (Blanke et al., 2008) |
Initial accelerated approval | |||||||
EORTC Study STSBG62005 | 3 | N = 946 | Imatinib daily versus BID | PFS at median 760 day follow-up: 56% (one daily) versus 50% (twice daily)* | CR: 5%, no significant difference between groups | (Verweij et al., 2004) | |
Ph+ ALL, relapsed/refractory | 2 | N = 48 | Imatinib | CHR: 19% | TTP 2.2 months | (Ottmann et al., 2002) | |
OS: 4.9 months | |||||||
MDS/MPD, with PDGFR rearrangement | NA | Phase 2/case reports, N = 31 | Imatinib | CHR 45% | PI | ||
MCyR: 39% | |||||||
ASM without c-Kit mutation/unknown c-Kit status | NA | Phase 2/case reports, N = 28 | Imatinib | CHR: 29% | PI | ||
Partial hematological response: 32% | |||||||
HES/CEL, with FIP1L1-PDGFRalpha or unknown status | NA | Phase 2/case reports, N = 176 | Imatinib | CHR: 61% | PI | ||
Partial hematological response: 13% | |||||||
DFSP, unresectable/recurrent/metastatic | NA | Phase 2/case reports, N = 18 | Imatinib | CR: 39% | PI | ||
PR: 44% | |||||||
Ipilimumab | |||||||
Melanoma, unresectable/metastatic | 3 | N = 676 | Ipilimumab with gp100 vaccine, versusipilumimab versus vaccine | OS: 10.0 months (combination) * versus 10.1 months (ipilimumab)* versus 6.4 months (gp100) | ORR: 10.9% (ipilimumab)* versus 5.7% (combination)* versus 1.5% (gp 100 alone) | (Hodi et al., 2010) | |
Lapatinib | |||||||
HER2+ breast cancer, locally advanced or metastatic, with capecitabine, after prior therapy | N = 399 | Capecitabine with versus without lapatinib | TTP: 8.4 versus 4.4 months* | ORR: 22% versus 14%* | (Cameron et al., 2010; Geyer et al., 2006) | ||
OS, adjusted for crossover: 75 versus 56.4 weeks* | |||||||
HER2+, HR+ breast cancer, metastatic, with letrozole, for postmenopausal women in whom hormonal therapy is indicated | 3 | N = 1286 (219 HER2+ patients) | Letrozole with versus without lapatinib | PFS (HER2+): 35.4 versus 13.0 weeks* | ORR (HER2+): 27.9 versus 14.8%* | (Schwartzberg et al., 2010), PI | |
Accelerated approval | |||||||
Nilotinib | |||||||
Ph+ CML-CP, newly diagnosed | ENESTnd | 3 | N = 846 | Nilotinib 300 or 400 mg PO BID versus imatinib | 12 month MMR: 44% (300 mg nilotinib)* versus 43% (400 mg nilotinib)* versus 22% (imatinib) | CCyR at 12 months: 80% (nilotinib 300 mg)* versus 78% (nilotinib 400 mg) * versus 65% (imatinib) | (Larson et al., 2012; Saglio et al., 2010b) |
Accelerated approval | OS at 3 years: no significant difference | ||||||
Ph+ CML, CP or AP, imatinib resistant/intolerant | 2 | N = 321(CP cohort) and 137 (AP cohort) | Nilotinib | CP: MCyR: 59% | CML - CP: | (le Coutre et al., 2008, 2012; Kantarjian et al., 2007b, 2011) | |
Accelerated approval | AP: Hematological response: 55% | CCyR: 44% | |||||
Est OS, at 24 months: 87% | |||||||
CML - AP: | |||||||
CCyR 21% | |||||||
Est OS at 24 months: 70% | |||||||
Ofatumumab | |||||||
CLL, relapsed/refractory | NS | N = 154 | Ofatumumab | ORR: 42% | DR: 6.5 months | (Wierda et al., 2010), PI | |
Accelerated approval | |||||||
1/2 | N = 33 | Ofatumumab dose escalation | ORR: 44% | (Coiffier et al., 2008) | |||
Ponatinib | |||||||
CML or Ph+ ALL, resistant or intolerant to tyrosine kinase inhibitor therapy | PACE | 2 | N = 444 | Ponatinib | MCyR | Time to MCyR: | (Cortes et al., 2012) |
Accelerated approval | CML-CP: 54% | CML-CP: 84 days | |||||
MaHR: | Duration of MaHR: | ||||||
CML-AP:52% | CML-AP: 9.5 months | ||||||
CML-BP: 31% | CML-BP: 4.7 months | ||||||
Ph+ ALL: 41% | Ph+ ALL: 3.2 months | ||||||
Panitumumab | |||||||
Metastatic CRC, K-RAS WT, single agent, after progression on fluoropyrimidine, oxaliplatin, and irinotecan | 3 | N = 463 | Panitumomab versus BSC | PFS: 8 weeks versus 7.3 weeks* | ORR: 10% versus 0%* | (Amado et al., 2008; Van Cutsem et al., 2007) | |
Retrospective: | OS, K-RAS WT: 8.1 versus 7.6 months* | ||||||
K-RAS WT: 12.3 versus 7.3 weeks* | |||||||
K-RAS+: 7.4 versus 7.3 weeks | |||||||
Pazopanib | |||||||
Advanced RCC | 3 | First-line or cytokine refractory, N = 435 | Pazopanib versus placebo | PFS: 9.2 versus 4.2 months* | ORR: 30% versus 3%* | (Sternberg et al., 2010) | |
Advanced soft tissue sarcoma, after prior chemotherapy | PALETTE | 3 | N = 369 | Pazopanib versus placebo | PFS: 4.6 versus 1.6 months* | OS: 12.5 months versus 10.7 months | (van der Graaf et al., 2012) |
Pertuzumab | |||||||
Metastatic breast cancer, HER2+, no prior HER2 therapy or chemotherapy for metastatic disease, with trastuzumab/docetaxel | CLEOPATRA | 3 | N = 808 | Trastuzumab plus docetaxel, with versus without pertuzumab | PFS: 18.5 months versus 12.4 months* | OS (median 19.3 month follow-up): 23.6% versus 17.2%* | (Baselga et al., 2012b) |
Rituximab | |||||||
Low-grade/follicular NHL, after response to first-line induction | PRIMA | 3 | After response to rituximab + chemotherapy, N = 1018 | Rituximab maintenance versus observation | PFS at mean 36 months follow-up: 74.9% versus 57.6%* | OS: no significant difference | (Salles et al., 2011) |
ECOG 1496 | 3 | N = 311 | CVP followed by rituximab versus observation | PFS: 4.3 versus 1.3 years* | 3-year OS: 92% versus 86%* | (Hochster et al., 2009) | |
Follicular lymphoma, previously untreated | 3 | N = 321 | CVP chemotherapy with versus without rituximab | TTF: 27 versus 7 months* | CR: 30% versus 8%* | (Marcus et al., 2005) | |
TTP: 32 versus 15 months* | |||||||
Follicular/low-grade NHL, relapsed/refractory | NS | N = 166 | Rituximab | ORR 48% | (McLaughlin et al., 1998) | ||
Estimated TTP: 12.5 months | |||||||
2 | N = 37 | Rituximab | ORR 57% | (Piro et al., 1999) | |||
TTP: not reached at 19.4 months. | |||||||
2 | N = 60 | Rituximab | ORR 40% | (Davis et al., 2000) | |||
Estimated TTP: 17.8 months | |||||||
DLBCL, in combination with CHOP or anthracycline-based chemotherapy | MInT Study | 3 | Age 18–60 years, N = 824 | CHOP-like chemotherapy+/− rituximab | 3-year event-free survival: 79% versus 59%* | OS, at 3 years: 93% versus 84%* | (Pfreundschuh et al., 2006) |
ECOG 4494 trial | 3 | Age 60–80, N = 632 | CHOP with versus without rituximab | 3-year FFS: 53% versus 46%* | PFS, adjusted: 3.1 versus 1.6 years* | (Habermann et al., 2006), PI | |
OS, 2 year, adjusted: 74% versus 63%* | |||||||
GELA/LNH-98.5 | 3 | Age 60–80, N = 399 | CHOP with versus without rituximab | EFS, at median 24 months: 57% versus 49%* | OS: 8.4 versus 3.5 years* | (Coiffier et al., 2002) | |
Previously untreated follicular NHL or DLBCL, as 90-minute infusion | RATE | NS | N = 363 | Follicular lymphoma: R- CVP | Grade 3–4 infusion reactions: 2.8% starting at cycle 2 | c | |
DLBCL: R-CHOP | |||||||
CLL | 3 | CLL, previously untreated, N = 817 | Fludarabine/cyclophosphamide with versus without rituximab | PFS at 3 years: 65% versus 45%* | OS at 3 years: 87% versus 83% | (Hallek et al., 2010) | |
REACH | 3 | CLL, previously treated, N = 552 | Fludarabine/cyclophosphamide with versus without rituximab | PFS: 27 versus 21.9 months* | OS: No significant difference, crossover design | (Robak et al., 2010) | |
ORR: 69.9% versus 58%* | |||||||
Regorafenib | |||||||
Metastatic CRC, previously treated with fluoropyrimidine/oxaliplatin/irinotecan-based chemotherapy, VEGF therapy and anti-EGFR therapy if K-RAS WT | CORRECT | 3 | N = 760 | Regorafenib versus placebo | OS: 6.4 versus 5.0 months* | PFS: 2.0 versus 1.7 months* | (Grothey et al., 2013), PI |
ORR: 1% versus 0.4% | |||||||
Romidepsin | |||||||
CTCL after at least one prior systemic therapy | 2 | N = 96 | Romidepsin | ORR: 34% | DR: 15 months | (Whittaker et al., 2010) | |
Improved pruritus: 43%, median duration 6 months | |||||||
2 | N = 71 | Romidepsin | ORR: 34% | (Piekarz et al., 2009) | |||
CRR 7% | |||||||
DR: 13.7 months | |||||||
PTCL, after at least one prior therapy | 2 | N = 130 | Romidepsin | CR+CRu: 14.6% (95% CI 9%–21.9%) | ORR: 25.4% | (Coiffier et al., 2012) | |
Accelerated approval | TTR: 1.9 months | ||||||
DR: 16.6 months | |||||||
2 | N = 47 | Romidepsin | ORR: 38% (95% CI 24%–53%) CR: 18% | DR: 8.9 months | (Piekarz et al., 2011) | ||
Ruxolitinib | |||||||
Intermediate or high-risk myelofibrosis | COMFORT-I | 3 | N = 309 | Ruxolitinib versus placebo | Spleen volume decreased by >35% at 24 weeks: 41.9% versus 0.7% * | Symptom improvement: 45.9% versus 5.3%* | (Verstovsek et al., 2012) |
OS at median 51 weeks: 91.6% versus 84.4%* | |||||||
COMFORT-II | 3 | N = 219 | Ruxolitinib versus best available therapy | Spleen volume decreased by >35%, at 48 weeks: 28 versus 0%* | No significant difference in TTP or OS at 48-week follow-up | (Harrison et al., 2012) | |
Sorafenib | |||||||
Advanced RCC | TARGET | 3 | Refractory to standard therapy, N = 903 | Sorafenib versus placebo | OS: 14.7 months versus not reached* | PFS: 5.5 versus 2.8 months* | (Escudier et al., 2007b) |
2 | Refractory to standard therapy, N = 202 | Sorafenib versus placebo | PFS at 24 weeks: 50% versus 18%* | PFS: 24 versus 6 weeks* | (Ratain et al., 2006) | ||
Unresectable HCC | SHARP | 3 | No prior systemic treatment, N = 602 | Sorafenib versus placebo | OS: 10.7 versus 7.9 months* | Time to radiological progression: 5.5 versus 2.8 months* | (Llovet et al., 2008) |
Time to symptomatic progression: 4.9 versus 4.1 months | |||||||
Sunitinib | |||||||
GIST, after imatinib resistance/intolerance | 3 | N = 312 | Sunitinib versus placebo | TTP: 27.3 versus 6.4 weeks* | PFS: 24.1 versus 6 weeks* | (Demetri et al., 2006) | |
NS | N = 55 | Sunitinib dose escalation | PR: 9.1% | PI | |||
Advanced RCC | 3 | No prior treatment, N = 750 | Sunitinib versus IFN-α | PFS: 11 versus 5 months* | ORR: 31% versus 6%* | (Motzer et al., 2007) | |
Initial accelerated approval | |||||||
2 | Refractory to cytokines, N = 106 | Sunitinib | ORR: 34% | PFS: 8.3 months | (Motzer et al., 2006a) | ||
2 | Refractory to cytokines, N = 63 | Sunitinib | ORR: 40% PR | TTP: 8.7 months | (Motzer et al., 2006b) | ||
OS: 16.4 months | |||||||
PNET, unresectable or metastatic | 3 | N = 171 | Sunitinib versus placebo | PFS: 11.4 versus 5.5 months* | ORR: 9.3% versus 0%* | (Raymond et al., 2011) | |
OS at 6 months: 92.6% versus 85.2%* | |||||||
Temsirolimus | |||||||
Advanced RCC | 3 | Metastatic RCC, N = 626 | Temsirolimus versus IFN-α versus combination | OS: 10.9 months (temsirolimus)* versus 7.3 months (IFN) versus 8.4 months (combination) | ORR: 8.6% (temsirolimus) versus 4.8% (IFN) versus 8.1% (combination) | (Hudes et al., 2007) | |
Tositumomab | |||||||
Relapsed/refractory CD20+ NHL, progression after/on rituximab | 2 | N = 40 | Tositumomab therapeutic regimen | ORR: 68% | PFS: 10.4 months | (Horning et al., 2005) | |
CR: 33% | |||||||
DR: 16 months | |||||||
Trastuzumab | |||||||
Metastatic gastric or GE junction adenocarcinoma, HER2+ | ToGA | 3 | Previously untreated for metastatic disease, N = 594 | Capecitabine or fluorouracil, with cisplatin, with versus without trastuzumab | OS: 13.8 versus 11,1 months* | PFS: 6.7 versus 5.5 months* | (Bang et al., 2010) |
Breast cancer, HER2+, adjuvant | NCCTG N9831; NSABP B-31 | 3 | N = 3351 | Doxorubicin/cyclophosphamide with paclitaxel, with versus without trastuzumab | Disease-free survival, median 4-month follow-up: 85.3% versus 67.1%* | OS at 4 years: 91.4% versus 86.6%* | (Romond et al., 2005) |
HERA | 3 | N = 3401 | Trastuzumab versus observation | DFS at 4 years: 78.6% versus 72.2%* | OS at 4 years: 89.3% versus 87.7% | (Gianni et al., 2011; Piccart-Gebhart et al., 2005) | |
BCIRG 006 | 3 | N = 3222 | AC-T (doxorubicin + cyclophosphamide and docetaxel q3 weeks) versus AC-T with trastuzumab for 52 weeks versus docetaxel and carboplatin with trastuzumab for 52 weeks (TCH) | DFS at 5 years (estimated): 75% (AC-T), 84% (AC-T + trastuzumab) * versus 81% (TCH) * | OS at 5 years (estimated): 87% (AC-T) versus 92% (AC-T + trastuzumab) versus 91% (TCH) * | (Slamon et al., 2011) | |
HER2+ breast cancer, metastatic | H0648g | 3 | Previously untreated, N = 469 | Paclitaxel or AC with versus without trastuzumab | TTP: 7.2 versus 4.5 months* | ORR: 45% versus 29%* | (Eiermann, 2001; Slamon et al., 2001),PI |
OS: 25.1 versus 20.3 months* | |||||||
H0649g | 2 | Progressive despite 1–2 prior chemotherapy regimens, N = 222 | Trastuzumab | ORR: 15% | DR: 9.1 months | (Cobleigh et al., 1999) | |
OS: 13 months | |||||||
Trastuzumab-DM1 | |||||||
Metastatic breast cancer, HER2 +, second-line after prior treatment with trastuzumab and a taxane | EMILIA | 3 | N = 991 | Trastuzumab-DM1 versus lapatinib with capecitabine | PFS: 9.6 versus 6.4 months* | ORR: 43.6% versus 30.8%* | (Verma et al., 2012) |
OS: 30.9 versus 25.1 months* | |||||||
Vandetanib | |||||||
Medullary thyroid cancer, symptomatic or progressive, and unresectable/metastatic | ZETA | 3 | N = 331 | Vandetanib versus placebo | PFS: 30.5 versus 19.3 months* | ORR: 45% versus 13%* | (Wells et al., 2010, 2012) |
Vemurafenib | |||||||
Melanoma, with the BRAF V600E mutation, unresectable or metastatic | BRIM3 | 3 | Previously untreated, N = 675 | Vemurafenib versus dacarbazine | OS at 6 months: 84% versus 64%* | ORR: 48% versus 5%* | (Chapman et al., 2011; Flaherty et al., 2010) |
PFS: 5.3 versus 1.6 months* | |||||||
BRIM2 | 2 | Previously treated, N = 132 | Vemurafenib | ORR at 12.9-month follow-up: 53% | DR: 6.7 months | (Sosman et al., 2012) | |
PFS: 6.8 months | |||||||
OS: 15.9 months | |||||||
Vismodegib | |||||||
BCC, metastatic or recurrent locally advanced, not surgical or radiation therapy candidate | ERIVANCE | 2 | N = 96 | Vismodegib | ORR: 30% (metastatic), 43% (locally advanced) | DR: 7.6 months | (Sekulic et al., 2012) |
PFS: 9.5 months | |||||||
Vorinostat | |||||||
CTCL, cutaneous manifestations, despite two prior systemic therapies | 2B | N = 74 | Vorinostat | ORR: 29.7% | DR: Est 185+ days | (Olsen et al., 2007) | |
2 | N = 33 | Vorinostat | ORR: 24.2% | DR: 15.1 weeks | (Duvic et al., 2007) | ||
Ziv-aflibercept | |||||||
Metastatic CRC, with FOLFIRI, after progression on an oxaliplatin-containing regimen | VELOUR | 3 | N = 1226 | FOLFIRI with Ziv-aflibercept versus placebo | OS: 13.5 versus 12.06 months* | PFS: 6.90 versus 4.67 months* | PId |
ORR: 19.8% versus 11.1%* |
AC, anthracycline plus cyclophosphamide; AC-T, anthracycline, cyclophosphamide, taxol; ALL, acute lymphoblastic leukemia; AP, accelerated phase; ASM, aggressive systemic mastocytosis; BCC, basal cell carcinoma; B-CLL, B cell CLL; BID, twice daily; BP, blast phase; BSC, best supportive care; CCyR, complete cytogenetic response; CEL, chronic eosinophilic leukemia; CHOP, cyclophosphamide, hydroxyldaunorubicin, oncovin, and prednisone; CHR, complete hematological response; CP, chronic phase; CR, complete response; CRu, unconfirmed complete response; CTCL, cutaneous T-cell lymphoma; CVP, cyclophosphamide, vincristine, and prednisone; DFS, disease-free survival; DFSP, dermatofibrosarcoma protuberans; DLBCL, diffuse large B cell lymphoma; DR, disease recurrence; EFS, event-free survival; FFS, failure-free survival; 5-FU, 5-fluorouracil; FOLFIRI, leucovorin, fluorouracil, irinotecan; FOLFOX, leucovorin, fluorouracil, oxaliplatin; GE, gastroesophageal; HCC, hepatocellular carcinoma; HES, hypereosinophilic syndrome; HR, hazard ratio; IFN-α, interferon-α; LB, lymphoid blast; LV, leucovorin; MaHR, major hematological response; MB, myeloid blast; MCyR, major cytogenetic response; MDS, myelodysplastic syndromes; MMR, major molecular response; MPD, myeloproliferative disease; N/A, not applicable; NHL, non–Hodgkin's lymphoma; NS, not significant; OHR, overall hematological response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PI, package information, package insert; PO, by mouth; PR, partial response; PTCL, peripheral T cell lymphoma; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; R-CVP, rituximab, cyclophosphamide, vincristine, prednisone; RFS, recurrence-free survival; RR, response rate; sALCL, systemic anaplastic large-cell lymphoma; SCCHN, squamous cell carcinoma of the head and neck; SCT, stem cell transplant; SEGA, subependymal giant cell astrocytoma; SQ, subcutaneous; TCH, docetaxel, carboplatin, trastuzumab; TSC, tuberous sclerosis complex; TTF, time to treatment failure; TTP, time to progression; TTR, time to recurrence.
↵a Crinò et al., 2011.
↵b Camidge et al., 2011.
↵c Dakhil et al., 2011.
↵d Joulain et al., 2012.
↵* Statistically significant difference (P < 0.05).