Chemotherapy and/or bevacizumab

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy):

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy):

The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy): › The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

Pegylated liposomal doxorubicin 40 mg/m2 by IV on day 1 every 4 weeks.

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy): › The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

Paclitaxel 80 mg/m2 by IV on days 1, 8, 15, and 22 every 4 weeks.

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy): › The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

Topotecan 4 mg/m2 by IV on days 1, 8, and 15 every 4 weeks; or 1.25 mg/m2 by IV on days 1 through 5 every 3 weeks.

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy): › The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

Patients in the bevacizumab arm exhibited longer PFS (HR, 0.48; 95% CI, 0.38 to 0.60); median PFS was 3.4 months in the chemotherapy-alone arm versus 6.7 months in the chemotherapy-plus-bevacizumab arm.

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy): › The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

The objective response rate was 12.6% in the chemotherapy-alone arm versus 30.9% in the chemotherapy-plus-bevacizumab arm.

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy): › The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

There was no statistically significant difference in OS between the regimens (13.3 months chemotherapy alone vs. 16.6 months chemotherapy plus bevacizumab).

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy): › The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

Patients in the chemotherapy-plus-bevacizumab arm had an increased incidence of hypertension and proteinuria, when compared with patients in the chemotherapy-only arm.

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy): › The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

GI perforation occurred in 2% of those receiving chemotherapy plus bevacizumab, which reflects the study’s stringent exclusion criteria.

Chemotherapy with or without bevacizumab. The FDA has approved the use of bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan as a result of the OCEANS and AURELIA trials. OCEANS (NCT00434642) assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences. For more information, see the Bevacizumab, other targeted drugs, and poly (ADP-ribose) polymerase (PARP) inhibitors with or without chemotherapy section. Evidence (bevacizumab with chemotherapy): › The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA [NCT00976911]) trial was an open-label, randomized trial designed to evaluate the effect of adding bevacizumab to standard chemotherapy in patients with platinum-resistant recurrent ovarian cancer.[68] Eligible patients had platinum-resistant disease (progression within 6 months of finishing a regimen) and no more than two previous regimens. Patients with platinum-refractory disease (those with progression during receipt of a platinum-containing regimen) and those with clinical or radiological signs of bowel involvement were ineligible. Patients were prescribed one of the following three chemotherapy regimens, on the basis of physician preference:Patients were then randomly assigned to receive either chemotherapy alone or chemotherapy with bevacizumab (10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks if on the 3-week-dosing schedule). Crossover to a bevacizumab-containing regimen was allowed at progression for those patients in the chemotherapy-only arm. PFS was the primary outcome, with response rate, OS, safety, and quality of life used as secondary end points. The enrollment included 361 patients with a median follow-up of 13.9 months in the chemotherapy-only arm and 13.0 months in the chemotherapy-plus-bevacizumab arm. Although there were some limitations in study design,[70] more patients on the chemotherapy-plus-bevacizumab arm had 15% or greater improvement in their GI scores when compared with baseline. For the chemotherapy-plus-bevacizumab arm, 34 of 115 patients (29.6%) showed improvement versus 15 of 118 (12.7%) patients who showed improvement on the chemotherapy-alone arm (difference, 16.9%; 95% CI, 6.1%–27.6%; P = .002).These studies confirm the effect of improving PFS when bevacizumab is added to chemotherapy for ovarian cancer. In the OCEANS trial, the HR for progression was even more prominent than in the first-line trials, and a significant effect was seen when the bevacizumab-chemotherapy combination was extended beyond six cycles until progression.In summary, the improvement achieved by bevacizumab in relative risk and PFS rates in platinum-sensitive and platinum-resistant recurrences has been consistently more than the improvement achieved with chemotherapy alone; however, bevacizumab-related toxic effects must be considered.

The primary end point for the quality-of-life portion of the study was a 15% or greater absolute improvement in the abdominal and GI symptom portion of the assessment modules at week 8 to week 9 of the protocol for patients in the chemotherapy-plus-bevacizumab arm.[69][Level of evidence A3] The study used patient-reported outcomes from the European Organisation for Research and Treatment of Cancer Ovarian Cancer Module 28 and the Functional Assessment of Cancer Therapy-Ovarian Cancer symptom index at baseline and every 8 to 9 weeks until disease progression.

Bevacizumab alone. Three phase II studies have shown activity for this antibody to vascular endothelial growth factor.

Bevacizumab alone. Three phase II studies have shown activity for this antibody to vascular endothelial growth factor.

The first study (GOG-0170D) included 62 patients who had received only one or two previous treatments. These last patients had received one additional platinum-based regimen because of an initial interval of 12 months or longer after first-line regimens and also had to have a performance status of 0 or 1.[71] Patients received a dose of 15 mg/kg every 21 days.

Bevacizumab alone. Three phase II studies have shown activity for this antibody to vascular endothelial growth factor. › The first study (GOG-0170D) included 62 patients who had received only one or two previous treatments. These last patients had received one additional platinum-based regimen because of an initial interval of 12 months or longer after first-line regimens and also had to have a performance status of 0 or 1.[71] Patients received a dose of 15 mg/kg every 21 days.

There were two complete responses and 11 partial responses, a median PFS of 4.7 months, and an OS of 17 months. This activity was noted in both platinum-sensitive and platinum-resistant subsets.

Bevacizumab alone. Three phase II studies have shown activity for this antibody to vascular endothelial growth factor.

The second study included only patients with platinum-resistant disease using an identical dose schedule.

Bevacizumab alone. Three phase II studies have shown activity for this antibody to vascular endothelial growth factor. › The second study included only patients with platinum-resistant disease using an identical dose schedule.

The study was stopped because 5 of 44 patients experienced bowel perforations, one of them fatal; seven partial responses had been observed.[72] This increased risk of bowel perforations was associated with three or more previous treatments.[73-75][Level of evidence C2]

Bevacizumab alone. Three phase II studies have shown activity for this antibody to vascular endothelial growth factor.

The third study (CCC-PHII-45) included 70 patients who received 50 mg of oral cyclophosphamide daily, in addition to bevacizumab (10 mg/kg q 2 weeks).

Bevacizumab alone. Three phase II studies have shown activity for this antibody to vascular endothelial growth factor. › The third study (CCC-PHII-45) included 70 patients who received 50 mg of oral cyclophosphamide daily, in addition to bevacizumab (10 mg/kg q 2 weeks).

Partial responses were observed in 17 patients, and 4 patients had intestinal perforations.[76]