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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

Published:August 31, 2018DOI:https://doi.org/10.1016/j.ygyno.2018.08.027

      Highlights

      • Bevacizumab monotherapy is active therapy for recurrent ovarian cancer, but resistance is common.
      • BV + EV combination had a higher measurable response (22% vs 12%) compared to BV alone.
      • BV + EV combination had higher toxicity and study removal (29% vs 12%) compared to BV alone.
      • BV + EV combination did not improve progression free or overall survival.

      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.

      Keywords

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