In the phase III MITO16b/MANGO–OV2/ENGOT–ov17 trial, investigators found that treatment with a carboplatin-based doublet plus bevacizumab beyond disease progression significantly improved progression-free survival vs a carboplatin-based doublet alone in women with platinum-sensitive ovarian cancer who experienced disease recurrence after first-line treatment with a platinum-based therapy plus bevacizumab. The study was reported in The Lancet Oncology by Sandro Pignata, MD, and colleagues.

Sandro Pignata, MD

As stated by the investigators, “Bevacizumab is approved in combination with chemotherapy for the treatment of ovarian cancer, either in first-line therapy or for patients with recurrent disease not previously treated with the same drug. We aimed to test the value of continuing bevacizumab beyond progression after first-line treatment with the same drug.”

Study Details

The open-label trial included 406 women from sites in Italy, France, Switzerland, and Greece who had previously received first-line platinum-based therapy including bevacizumab and had recurrent (≥ 6 months since last platinum dose) stage IIIB to IV disease. Patients were randomly assigned between December 2013 and November 2016 to receive a carboplatin-based doublet plus continued bevacizumab (bevacizumab group, n = 203) or a carboplatin-based doublet alone (control group, n = 203).

Chemotherapy consisted of investigator’s choice, selected prior to random assignment, of:

• Carboplatin at area under the curve (AUC) = 5 on day 1 plus paclitaxel at 175 mg/m² on day 1 every 21 days
• Carboplatin AUC = 4 on day 1 plus gemcitabine at 1,000 mg/m² on days 1 and 8 every 21 days
• Carboplatin AUC = 5 on day 1 plus pegylated liposomal doxorubicin at 30 mg/m² on day 1 every 28 days.

Bevacizumab was given at 10 mg/kg every 14 days when combined with pegylated liposomal doxorubicin/carboplatin or at 15 mg/kg every 21 days when combined with gemcitabine/carboplatin or paclitaxel/carboplatin. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population.

Progression-Free Survival

Median follow-up was 20.1 months (interquartile range = 12.9–27.8 months). Median progression-free survival was 11.8 months (95% confidence interval [CI] = 10.8–12.9 months) in the bevacizumab group vs 8.8 months (95% CI = 8.4–9.3 months) in the control group (hazard ratio [HR] = 0.51, 95% CI = 0.41–0.65, P < .0001). Hazard ratios favored the bevacizumab group in all subgroups examined except for the subgroup of 53 patients with BRCA1 or BRCA2 mutations: hazard ratios were 0.36 (95% CI =0.25–0.50) among 203 patients with wild-type BRCA and 1.58 (95% CI = 0.667–3.71) among those with mutations (P = .0004 for interaction).

Among 130 vs 143 patients eligible for objective response rate analysis, objective response was observed in 69.2% vs 49.7% of patients (P = .001). Median overall survival was 26.7 months (95% CI = 22.7–30.5 months) vs 27.1 months (95% CI = 22.0 months–not reached; HR = 0.99, 95% CI = 0.73–1.39, P < .98).

Adverse Events

Grade ≥ 3 adverse events occurred in 79% of patients in the bevacizumab group vs 69% in the control group, with the most common in the bevacizumab group being decreased neutrophil count (40% vs 41% in control group), decreased platelet count (30% vs 22%), and hypertension (29% vs 10%). Grade 3 to 4 proteinuria occurred in 4% vs 0%. Serious adverse events occurred in 26% vs 20% of patients. Death considered related to treatment occurred in one patient in the bevacizumab group and two patients in the control group.

The investigators concluded, “Continuing bevacizumab beyond progression combined with chemotherapy in patients with platinum-sensitive recurrent ovarian cancer improves progression-free survival compared with standard chemotherapy alone and might be considered in clinical practice.”

Dr. Pignata, of the Istituto Nazionale per lo Studio e la Cura dei Tumori IRCCS Fondazione Pascale, Naples, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Hoffmann–La Roche and Associazione Italiana per la Ricerca sul Cancro. For full disclosures of the study authors, visit thelancet.com.