Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer.

PURPOSE: To determine the effects of bevacizumab on patient-reported outcomes (PROs; secondary end point) in the AURELIA trial. PATIENTS AND METHODS: Patients with platinum-resistant ovarian cancer were randomly assigned to chemotherapy alone (CT) or with bevacizumab (BEV-CT). PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module 28 (EORTC QLQ-OV28) and Functional Assessment of Cancer Therapy-Ovarian Cancer symptom index (FOSI) at baseline and every two or three cycles (8/9 weeks) until disease progression. The primary PRO hypothesis was that more patients receiving BEV-CT than CT would achieve at least a 15% (≥ 15-point) absolute improvement on the QLQ-OV28 abdominal/GI symptom subscale (items 31-36) at week 8/9. Patients with missing week 8/9 questionnaires were included as unimproved. Questionnaires from all assessments until disease progression were analyzed using mixed-model repeated-measures (MMRM) analysis. Sensitivity analyses were used to determine the effects of differing assumptions and methods for missing data. RESULTS: Baseline questionnaires were available from 89% of 361 randomly assigned patients. More BEV-CT than CT patients achieved a ≥ 15% improvement in abdominal/GI symptoms at week 8/9 (primary PRO end point, 21.9% v 9.3%; difference, 12.7%; 95% CI, 4.4 to 20.9; P = .002). MMRM analysis covering all time points also favored BEV-CT (difference, 6.4 points; 95% CI, 1.3 to 11.6; P = .015). More BEV-CT than CT patients achieved ≥ 15% improvement in FOSI at week 8/9 (12.2% v 3.1%; difference, 9.0%; 95% CI, 2.9% to 15.2%; P = .003). Sensitivity analyses gave similar results and conclusions. CONCLUSION: Bevacizumab increased the proportion of patients achieving a 15% improvement in patient-reported abdominal/GI symptoms during chemotherapy for platinum-resistant ovarian cancer.

Overall survival in patients with metastatic renal cell carcinoma initially treated with bevacizumab plus interferon-α2a and subsequent therapy with tyrosine kinase inhibitors: a retrospective analysis of the phase III AVOREN trial.

OBJECTIVE: • To retrospectively evaluate the effect of subsequent tyrosine kinase inhibitors (TKIs) after first-line bevacizumab + interferon-α2a (IFN) or IFN + placebo in the phase III AVOREN (Avastin and Roferon in Renal Cell Carcinoma) trial. PATIENTS AND METHODS: • A total of 649 patients with untreated metastatic renal cell carcinoma (mRCC) were randomized to receive IFN (9 MIU three times a week for up to 1 year) in combination with bevacizumab (10 mg/kg every 2 weeks) or placebo until disease progression. • The protocol allowed the use of any post-protocol anti-cancer therapy for patients with progressive disease or those in whom the trial therapy was discontinued. Data regarding the timing and type of subsequent therapy were recorded and overall survival (OS) analysed. RESULTS: • Patients were randomized to bevacizumab + IFN (n= 327) or IFN + placebo (n= 322); 180 (55%) patients in the bevacizumab + IFN, and 202 (63%) in the IFN + placebo arm, received post-protocol anti-cancer therapy. • TKIs were the most common post-protocol therapy, received by 113 (35%) and 120 (37%) patients in the bevacizumab + IFN and IFN + placebo arms, respectively. • The median OS in patients who received any subsequent TKI was 38.6 months in the bevacizumab + IFN arm and 33.6 months in IFN + placebo arm [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.56-1.13; P= 0.203]. In an additional retrospective analysis that censored patients who received subsequent TKIs, median OS was 25.0 and 20.7 months, respectively, in the bevacizumab + IFN and IFN + placebo arms (HR, 0.84; 95% CI, 0.67-1.05; P= 0.123). CONCLUSIONS: • These retrospective exploratory data of sequential bevacizumab + IFN followed by TKIs in patients able to receive multiple lines of therapy suggest that sequential therapy could be a promising approach to improve patient outcomes in mRCC.

Prediction of progression-free survival rates after bevacizumab plus interferon versus interferon alone in patients with metastatic renal cell carcinoma: comparison of a nomogram to the Motzer criteria.

BACKGROUND: The combination of bevacizumab plus interferon (BEV+IFN) for treatment of metastatic renal cell carcinoma (mRCC) is associated with improved progression-free survival (PFS) in a phase 3 study. OBJECTIVE: To develop a novel model for prediction of individual PFS using data from the randomized, controlled phase 3 trial of BEV + IFN or interferon alone. The ability of the Motzer criteria for prediction of PFS was also assessed. DESIGN, SETTING, AND PARTICIPANTS: Pretreatment parameters of 628 patients were included in the Cox regression model predicting PFS at 6, 12, 18, and 24 mo. BEV+IFN was administered to 337 patients; 291 patients received interferon alone. The developed model and the Motzer criteria were internally validated using Harrell's concordance index and calibrated. RESULTS AND LIMITATIONS: Median PFS was 10.2 versus 4.6 mo (p < 0.001) for patients receiving BEV + IFN or interferon alone, respectively. The novel model relying on age, Karnofsky performance status, baseline albumin, alkaline phosphatase, and time from primary diagnosis to treatment resulted in the highest discrimination (area under the curve [AUC]: 72.8, 75.0, 72.8, and 70.8% at 6, 12, 18, and 24 mo). The AUC of the Motzer criteria risk groups was 63.7, 61.8, 58.6, and 51.8% for the same time points. Comparison of discriminatory ability between the developed model and the Motzer criteria showed statistically significant differences (all p ≤ 0.02). An external validation of the new model is warranted. CONCLUSIONS: The developed model identified prognostic factors of PFS in mRCC patients treated with BEV+IFN or interferon alone and quantified individual risk of PFS. Relative to the Motzer criteria, the novel model demonstrated better discriminatory properties. The model may serve clinicians in identifying patients who can benefit the most from BEV+IFN versus interferon alone.

Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival.

PURPOSE: A phase III trial of bevacizumab combined with interferon alfa-2a (IFN) showed significant improvements in progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC). Here, we report overall survival (OS) data. PATIENTS AND METHODS: Six hundred forty-nine patients with previously untreated mRCC were randomly assigned to receive bevacizumab (10 mg/kg every 2 weeks) plus IFN (9 MIU subcutaneously three times a week; n = 327) or IFN plus placebo (n = 322) in a multicenter, randomized, double-blind, phase III trial. The primary end point was OS. Final analysis of the secondary end point (PFS) was reported earlier. RESULTS: Median OS was 23.3 months with bevacizumab plus IFN and 21.3 months with IFN plus placebo (unstratified hazard ratio [HR] = 0.91; 95% CI, 0.76 to 1.10; P = .3360; stratified HR = 0.86; 95% CI, 0.72 to 1.04; P = .1291). Patients (> 55%) in both arms received at least one postprotocol antineoplastic therapy, possibly confounding the OS analysis. Patients receiving postprotocol therapy including a tyrosine kinase inhibitor had longer median OS (bevacizumab plus IFN arm: 38.6 months; IFN plus placebo arm: 33.6 months; HR = 0.80; 95% CI, 0.56 to 1.13). Tolerability was similar to that reported previously. CONCLUSION: Bevacizumab plus IFN is active as first-line treatment in patients with mRCC. Most patients with mRCC receive multiple lines of therapy, so considering the overall sequence of therapy when selecting first-line therapy may optimize patient benefit.