Sustained OS Benefit With Bevacizumab Addition In Advanced Cervical Cancer

Treatment with bevacizumab plus chemotherapy provides a sustained overall survival advantage over chemotherapy alone in patients with metastatic, persistent or recurrent cervical cancer

medwireNews: Among women with advanced cervical cancer, adding bevacizumab to a chemotherapeutic regimen results in an overall survival (OS) benefit that is maintained over time, shows the final analysis of the GOG 240 trial. 

Based on a previous interim analysis that showed longer OS with versus without bevacizumab in this patient population, the Vascular endothelial growth factor inhibitor was approved by the US Food and Drug Administration and the European Medicines Agency, followed by approval in at least 60 countries. 

In the current analysis of the phase III trial, conducted after 50 months or more of maximum follow-up and reported in The Lancet, bevacizumab addition continued to offer a survival advantage in women with metastatic, persistent or recurrent cervical carcinoma. 

Specifically, median OS was 16.8 months for the 227 women who were randomly assigned to receive bevacizumab plus either cisplatin or topotecan alongside paclitaxel and 13.3 months for the 225 participants given chemotherapy alone, giving a significant hazard ratio of 0.77. 

The study authors point out that the OS curves remained separated at the final analysis despite 20 patients in the chemotherapy-alone group crossing over to receive bevacizumab after the interim results became available. 

“Given that advanced cervical cancer is a disease for which OS has been typically measured in months (eg, 7–12 months at best), these data indicate that antiangiogenesis therapy can have clinically meaningful therapeutic benefit in this population”, they write. 

Post-progression OS was comparable for the bevacizumab and chemotherapy-alone groups, at a median of 8.4 and 7.1 months, respectively, which the team says shows the lack of a rebound effect, that is, shorter survival after bevacizumab is stopped than after chemotherapy alone is stopped. 

Krishnansu Tewari, from the University of California, Irvine Medical Center in Orange, USA, and co-workers report that fistulas of any grade developed in 15% of bevacizumab-treated participants and in 1% of those given chemotherapy alone, all of whom had received prior radiotherapy. Grade 3 fistulas were observed in 13 women in the bevacizumab group and just one woman in the control group, but no fistulas resulted in surgical emergencies, sepsis or death. 

In a related comment, Susana Banerjee, from the Royal Marsden Hospital in London, UK, notes that the post-progression OS was “very low”, adding that “[t]reatment clearly needs to be improved beyond first-line systemic therapy and various promising approaches exist with a biological rationale, including maintenance therapy, immunotherapy, other Antiangiogenic-directed drugs, and targeting of homologous recombination deficiency with poly(ADP-ribose) polymerase inhibitors.” 

The other issue, she says, is access. The greatest need for the drug is in low-income countries, but “[b]evacizumab is out of reach for many in these regions, and in low-income communities within high-income countries, because of the cost”, Susana Banerjee writes. 

She continues: “Measures such as introduction of biosimilars, generic drugs, and reduced bevacizumab dose have the potential to reduce cost and hopefully have a positive effect on accessibility to antiangiogenic therapy. 

“For oncology communities to work together globally to reduce the disparities that exist surrounding access to new agents is imperative.” 

References 

Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet; Advance online publication 27 July 2017. doi: http://dx.doi.org/10.1016/S0140-6736(17)31607-0

Banerjee S. Bevacizumab in cervical cancer: a step forward for survival. Lancet; Advance online publication 27 July 2017. doi: http://dx.doi.org/10.1016/S0140-6736(17)31965-7

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