Adding Bevacizumab to Chemotherapy in Advanced Cervical Cancer


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Krishnansu S. Tewari, MD

Krishnansu S. Tewari, MD

As reported in The Lancet by Krishnansu S. Tewari, MD, of the University of California-Irvine Medical Center, and colleagues, the final overall survival results of the phase III Gynecologic Oncology Group 240 trial show continued benefit of the addition of bevacizumab (Avastin) to chemotherapy in patients with metastatic, persistent, or recurrent cervical carcinoma.

In the open-label trial, 452 patients were randomized 1:1:1:1 -between April 2009 and January 2012 to receive cisplatin plus -paclitaxel or topotecan plus paclitaxel with (n = 227) or without (n = 225) bevacizumab in 21-day cycles until disease progression, unacceptable toxic effects, voluntary withdrawal, or complete response. At a prior interim analysis (after 271 deaths), resulting in the 2014 approval of bevacizumab in this setting, median overall survival was 17.0 months in the bevacizumab-plus-chemotherapy group vs 13.3 months in the chemotherapy-alone group (hazard ratio [HR] = 0.71, = .004).

In the final analysis, after 348 deaths, median overall survival was 16.8 months in the bevacizumab plus chemotherapy group vs 13.3 months in the chemotherapy-alone group (HR = 0.77, = .007). Among patients not receiving previous pelvic radiotherapy, median overall survival was 24.5 vs 16.8 months (HR = 0.64, = .11). Median post–disease progression overall survival was 8.4 vs 7.1 months (HR = 0.83, = .06).

Any-grade fistula occurred in 15% of the bevacizumab plus chemotherapy group vs 1% of the chemotherapy-alone groups, with all patients in both groups with fistula having received previous radiotherapy. Grade 3 fistula occurred in 6% vs < 1%, respectively. No fistulas resulted in surgical emergencies, sepsis, or death.

The investigators concluded: “The benefit conferred by incorporation of bevacizumab is sustained with extended follow-up as evidenced by the overall survival curves remaining separated. After progression while receiving bevacizumab, we did not observe a negative rebound effect (ie, shorter survival after bevacizumab is stopped than after chemotherapy alone is stopped). These findings represent proof of concept of the efficacy and tolerability of antiangiogenesis therapy in advanced cervical cancer.”

Tewari KS, et al: Lancet 390:1654-1663, 2017.


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