Susana Campos, MD, MPH reviewing Tewari KS et al. N Engl J Med 2014 Feb 20.
Adding bevacizumab to chemotherapy significantly improved overall survival.
Several cytotoxic regimens are often employed in the management of patients with advanced cervical cancer. Regrettably, advanced cervical cancer does not have a sustained response to chemotherapy. Bevacizumab has single-agent activity in heavily pretreated, recurrent cervical carcinoma (J Clin Oncol 2009; 27:1069).
Now, investigators have used a 2×2 factorial design to evaluate the effectiveness of bevacizumab in conjunction with either a nonplatinum doublet (topotecan and paclitaxel) or a platinum doublet (cisplatin and paclitaxel) in 452 patients with metastatic, recurrent, or persistent cervical cancer. Most patients had recurrent disease (72%) and had previously received platinum-based chemoradiotherapy (>70%).
At a median follow-up of 20.8 months, the combined data for both chemotherapy regimens showed that overall survival (the primary endpoint) was superior with bevacizumab plus chemotherapy versus chemotherapy alone (17.0 vs. 13.3 months; hazard ratio, 0.71; P=0.004); the response rate was also higher with bevacizumab (48% vs. 36%; P=0.008).Incidence of grade 2 or higher hypertension, thromboembolic events, and gastrointestinal or genitourinary events was higher with bevacizumab. The survival benefit of bevacizumab was not associated with a significant reduction in health-related quality of life (QOL), as measured by three validated QOL instruments. Mortality was similar between the groups receiving the two regimens of chemotherapy alone.
Bevacizumab is the first biological therapeutic agent to have a clinically meaningful impact in cervical cancer. Given the economic burden of such novel agents, understanding which patients might benefit most from treatment is of the utmost importance. This trial included patients with squamous cell, adenocarcinoma, and other histologic subtypes. Whether patients with adenocarcinoma achieve the same degree of benefit as those with a squamous histology remains uncertain. In addition to identifying predicative and prognostic biomarkers, finding an antiangiogenic signature that can predict response to bevacizumab should be a focus of future studies. It is important to note that research continues to identify other actionable molecular aberrations that drive the tumorigenesis of cervical cancer, such as mutations in the PI3K pathway.
Dr. Campos is an Assistant Professor of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute in Boston.