Formal discussant Gottfried Konecny, MD, Associate Professor of Medicine, David Geffen School of Medicine at UCLA, also viewed the study as a game changer. He cited the strengths of the study, including its design, randomization with stratification, P values adjusted for multiple testing, and the fact that no crossover was allowed. Prognostic factors were well balanced in both arms. The control arm did not underperform, he said. Other strengths of the study include a strong translational component, detailed quality-of-life assessment, and exploratory subsets, which can provide rationales for future trials.

“Prior to this study, no regimen improved overall survival in advanced cervical cancer. Median overall survival barely reaches 12 months with the current standard of care. The results of this study are clinically meaningful and important, as bevacizumab extended survival up to 17 months,” Dr. Konecny said.

Important Distinction

An important point is that the study demonstrated a progression-free survival improvement that translated to improved overall survival. In studies of other cancers, bevacizumab improved progression-free survival but not overall survival, which is an important distinction. “This study demonstrates favorable outcomes with bevacizumab in terms of survival compared with other cancers in the first-line setting,” he emphasized.

Study limitations cited by Dr. Konecny include the lack of a cost-benefit analysis and no information on treatment withdrawal regarding chemotherapy or bevacizumab. Also, as only 17% of the patients had metastatic disease, results may not be applicable to that group of patients, he said.

Future Studies

Dr. Konecny agreed with Dr. Tewari that this trial paves the way for other studies on angiogenic inhibitors such as tyrosine kinase inhibitors. However, this effort is hampered by the lack of prospectively validated predictors, although several are under study, he continued. Furthermore, studies of antiangiogenic agents are needed in earlier-stage disease and in patients with positive lymph nodes to determine whether they improve survival.

“It is critical to extend the global reach of antiangiogenic therapies for women with cervical cancer. We need to develop strategies that will benefit the global population, because the disease burden is much greater in developing countries than in the United States,” he concluded. ■

Disclosure: Dr. Konecny reported no potential conflicts of interest.