Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: An NRG Oncology/Gynecologic Oncology Group study Journal Article
| Authors: | Tew, W. P.; Sill, M. W.; Walker, J. L.; Secord, A. A.; Bonebrake, A. J.; Schilder, J. M.; Stuckey, A.; Rice, L.; Tewari, K. S.; Aghajanian, C. A. |
| Article Title: | Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: An NRG Oncology/Gynecologic Oncology Group study |
| Abstract: | Purpose: Bevacizumab (BV) monotherapy leads to compensatory upregulation of multiple signaling pathways, resulting in mTOR activation. We evaluated combining BV and everolimus (EV), an mTOR kinase inhibitor, to circumvent BV-resistance in women with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer (OC). Patients and methods: Eligible OC patients had measurable (RECIST1.1) or detectable disease, 1–3 prior regimens, performance status (PS) 0–2, and no prior m-TOR inhibitor. All patients received BV 10 mg/kg IV every 2wks. Patients were randomized (1:1) to oral EV (10 mg daily) or placebo stratified by platinum-free interval (PFI), measurable disease and prior BV. Primary endpoint was progression-free survival (PFS); secondary endpoints included safety and response. Results: 150 patients were randomized to BV with (n = 75) and without (n = 75) EV. Arms were well-balanced for age (median 63: range 28–92), PS (0: 73%, 1–2: 27%), prior regimens (1: 37%, 2: 47%, 3: 16%), prior BV (11%), PFI (<6mos: 65%) and measurable disease (81%). The BV + EV vs BV median PFS was 5.9 vs 4.5 months (hazard ratio [HR] 0.95 (95% CI, 0.66–1.37, p = 0.39)). Median OS was 16.6 vs 17.3 months (HR 1.16 (95% CI, 0.72–1.87, p = 0.55). Objective measurable responses were higher with BV + EV (22% vs 12%). Study removal due to toxicity was higher with BV + EV (29% vs 12%). Toxicity (≥grade 3) from BV + EV were “other GI (mucositis)” (23 vs 1%) and “metabolic/nutrition” (19 vs. 7%); common ≥ grade 2 toxicities with BV + EV were cytopenia, nausea, fatigue and rash. Conclusion: The combination regimen (BV + EV) did not significantly reduce the hazard of progression or death relative to BV and was associated with higher rates of adverse events and study discontinuation when compared to BV alone. © 2018 Elsevier Inc. |
| Keywords: | adult; controlled study; treatment response; aged; major clinical study; overall survival; fatigue; neutropenia; cancer recurrence; bevacizumab; cancer combination chemotherapy; monotherapy; cancer patient; ovarian cancer; progression free survival; infection; phase 2 clinical trial; anemia; heart disease; kidney disease; nausea; randomized controlled trial; thrombocytopenia; vomiting; peripheral neuropathy; dyspnea; rash; thromboembolism; ovary carcinoma; mental disease; targeted therapy; skin disease; ca 125 antigen; connective tissue disease; double blind procedure; hematoma; digestive system perforation; gastrointestinal disease; hepatobiliary disease; metabolic disorder; everolimus; cytopenia; thorax disease; musculoskeletal disease; immunopathology; vascular disease; oral mucositis; respiratory tract disease; comparative effectiveness; ear disease; application site reaction; post treatment survival; nutritional disorder; very elderly; human; female; priority journal; article |
| Journal Title: | Gynecologic Oncology |
| Volume: | 151 |
| Issue: | 2 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2018-11-01 |
| Start Page: | 257 |
| End Page: | 263 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2018.08.027 |
| PUBMED: | 30177462 |
| PROVIDER: | scopus |
| PMCID: | PMC6350932 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 December 2018 -- Source: Scopus |
