Dataset Information

P08.09 Axitinib for the treatment of patients with recurrent glioblastoma, final results from a randomized phase II clinical trial

ABSTRACT: Abstract Background: vascular endothelial growth factor receptor (VEGFR) signal transduction mediates glioblastoma (GB) associated neo-angiogenesis. The AXIG trial (NCT01562197) is a randomized clinical trial that initially investigated the activity of axitinib as a monotherapy (AXI-arm) versus physicians best alternative choice of therapy (Duerinck et al. JNO Mar 2016) and following amendment versus axitinib plus lomustine (Duerinck et al. ASCO AM 2016). Methods: an updated pooled analysis was made of the clinical outcome of all patients who initiated treatment with axitinib mono-therapy or axitinib in combination with lomustine in the AXIG trial. Results: between August 2011 and July 2015, a total of 78 pts were enrolled in the trial and initiated treatment with axitinib monotherapy (N: 50; AXI) or axitinib plus lomustine (N: 28; AXILOM). Median age was 55y [range 18–80], 50M/28F, 19, 29, 19, 7 and 4 pts had a WHO-PS of 0, 1, 2, 3 and 4 respectively. Baseline characteristics were well balanced between study arms (AXI vs AXILOM). All pts had failed prior surgery, RT and TMZ. Thirteen pts in the AXI-arm crossed-over at the time of progression (AXIseqLOM). Treatment was generally well tolerated. AXILOM pts were at higher risk for grade 3/4 adverse events (most frequent gr3/4 AE on AXILOM vs AXI were: thrombocytopenia 3- vs 0 pts, hypertension 2 vs 2 pts, anorexia 3 vs 3 pts). The best overall tumor response (by RANO criteria) was 2 CR/ 11 PR/ 11 SD/ 26 PD in the AXI arm (BORR 26%) vs. 1 CR/ 9 PR/ 3 SD/ 13 PD in the AXILOM-arm (BORR 38%). Adding CCNU to axitinib after progression (AXIseqLOM) resulted in 1 pt experiencing PR and 8pts experiencing SD. Six-mths PFS and OS rates were respectively 26% (95% CI 14–38) vs 17% (95% CI 2–32), and 54% (95% CI 40–68) vs. 53% (95% CI 34–73) for pts treated in the AXI vs. AXILOM-arms; median PFS and OS were respectively 12 vs. 16 wks and 25 vs. 27 wks. When the time-to-second progression was taken into account for the 9 AXIseqLOM patients who experienced PR or SD following the addition of lomustine at first PD on axitinib, 6-mths PFS was 39% (95% CI 21–57). No significant correlation was found between clinical outcome measures and the MGMT promoter methylation status or IDH1/2 mutation status. Conclusion: Axitinib has single-agent activity in patients with recurrent GB; upfront combination of axitinib and LOM did not significantly increase progression-free or overall survival in patients with recurrent glioblastoma. Adding CCNU to axitinib after progression seems to result in improved PFS compared to upfront combination therapy.

SUBMITTER: Duerinck J

PROVIDER: S-EPMC5782638 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroudThe European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP.Materials and methodsThis phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age < 80 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0-2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8 Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2 Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) values > 0.2 ng/ml.ResultsA total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37-120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively.ConclusionA higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933).

Project description:BACKGROUND:No treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB. METHODS:Adult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ?8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ?8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint. RESULTS:Between June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0-1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events. CONCLUSION:The combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.

Project description:BackgroundWe assessed the efficacy and safety of bevacizumab (BEV) through multiple lines in patients with recurrent glioblastoma who had progressed after first-line treatment with radiotherapy, temozolomide, and BEV.Patients and methodsTAMIGA (NCT01860638) was a phase II, randomized, double-blind, placebo-controlled, multicenter trial in adult patients with glioblastoma. Following surgery, patients with newly diagnosed glioblastoma received first-line treatment consisting of radiotherapy plus temozolomide and BEV, followed by six cycles of temozolomide and BEV, then BEV monotherapy until disease progression (PD1). Randomization occurred at PD1 (second line), and patients received lomustine (CCNU) plus BEV (CCNU + BEV) or CCNU plus placebo (CCNU + placebo) until further disease progression (PD2). At PD2 (third line), patients continued BEV or placebo with chemotherapy (investigator's choice). The primary endpoint was survival from randomization. Secondary endpoints were progression-free survival in the second and third lines (PFS2 and PFS3) and safety.ResultsOf the 296 patients enrolled, 123 were randomized at PD1 (CCNU + BEV, n = 61; CCNU + placebo, n = 62). The study was terminated prematurely because of the high drop-out rate during first-line treatment, implying underpowered inferential testing. The proportion of patients receiving corticosteroids at randomization was similar (BEV 33%, placebo 31%). For the CCNU + BEV and CCNU + placebo groups, respectively, median survival from randomization was 6.4 versus 5.5 months (stratified hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.69-1.59), median PFS2 was 2.3 versus 1.8 months (stratified HR, 0.70; 95% CI, 0.48-1.00), median PFS3 was 2.0 versus 2.2 months (stratified HR, 0.70; 95% CI, 0.37-1.33), and median time from randomization to a deterioration in health-related quality of life was 1.4 versus 1.3 months (stratified HR, 0.76; 95% CI, 0.52-1.12). The incidence of treatment-related grade 3 to 4 adverse events was 19% (CCNU + BEV) versus 15% (CCNU + placebo).ConclusionThere was no survival benefit and no detriment observed with continuing BEV through multiple lines in patients with recurrent glioblastoma.Implications for practicePrevious research suggested that there may be value in continuing bevacizumab (BEV) beyond progression through multiple lines of therapy. No survival benefit was observed with the use of BEV through multiple lines in patients with glioblastoma who had progressed after first-line treatment (radiotherapy + temozolomide + BEV). No new safety concerns arose from the use of BEV through multiple lines of therapy.

Dataset Information

P08.09 Axitinib for the treatment of patients with recurrent glioblastoma, final results from a randomized phase II clinical trial

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets