GOG 240 establishes sustained OS benefit of bevacizumab in cervical cancer
The addition of bevacizumab to chemotherapy improved overall survival (OS) in women with metastatic, persistent, or recurrent cervical cancer, according to the final OS analysis of the Gynecologic Oncology Group (GOG) 240 trial, confirming the findings observed in the interim analysis.
At final analysis (after 348 deaths), patients on chemotherapy plus bevacizumab had significantly higher OS compared with patients on chemotherapy only (16.8 vs 13.3 months; hazard ratio [HR], 0.77, 95 percent confidence interval, 0.62–0.95; p=0.007). [Lancet 2017;doi:10.1016/S0140-6736(17)31607-0]
“[F]irst-line therapy using bevacizumab in the recurrent, persistent, or metastatic setting has clinical value … these data indicate that antiangiogenesis therapy can have clinically meaningful therapeutic benefit in this population,” said the researchers.
“At first glance, a 3.5-month improvement in [OS], although significant, might appear modest … however, this finding needs to be put into context of the specific disease – most women survive for only around 12 months,” said Dr Susana Banerjee from the Royal Marsden Hospital, London, UK, in a commentary. [Lancet 2017;doi:10.1016/S0140-6736(17)31965-7]
When differentiated by chemotherapy type, patients on cisplatin and paclitaxel plus bevacizumab had improved OS over cisplatin and paclitaxel only (HR, 0.73; p=0.04), while the addition of bevacizumab did not improve OS in patients on a topotecan plus paclitaxel regimen (HR, 0.80; p=0.15).
OS was comparable between chemotherapy plus bevacizumab and chemotherapy only groups in patients without previous pelvic radiotherapy treatment (24.5 vs 16.8 months; HR, 0.64; p=0.11).
Postprogression OS was comparable between patients on chemotherapy plus bevacizumab and chemotherapy only (8.4 vs 7.1 months; HR, 0.83; p=0.06), while progression-free survival improved with the addition of bevacizumab (8.2 vs 6.0 months; HR, 0.68; p=0.0002).
Fistulas occurred more frequently among patients on bevacizumab compared with chemotherapy only (15 percent vs 1 percent), including severe (grade 3) fistulas (6 percent vs <1 percent), though all patients affected had previously received radiotherapy and none of the fistulas resulted in sepsis, death, or surgical emergencies.
In the multicentre, open-label, phase III trial, 452 patients with GOG status 1–2 metastatic, persistent, or recurrent cervical carcinoma were randomized to receive intravenous chemotherapy (cisplatin [50 mg/m2 on day 1 or 2] plus paclitaxel [135 or 175 mg/m2 on day 1] or topotecan [0.75 mg/m2 on days 1–3] plus paclitaxel [175 mg/m2 on day 1]) with bevacizumab (15 mg/kg on day 1, mean age 48.9 years) or without (mean age, 46.5 years) in 21 day cycles. Seventy-five percent (n=337) of patients had previously received platinum-based radiosensitizing chemotherapy.
Twenty patients who previously received only chemotherapy crossed over to the bevacizumab group following the second interim analysis.
Treatment was discontinued in the instance of disease progression, unacceptable toxicity, complete response, or patient withdrawal. Disease progression was assessed by follow-up every 3 months for 2 years followed by every 6 months for 3 years after treatment discontinuation, while adverse events reported were within 30 days of final treatment administration.
According to Banerjee, identifying the patients who would most benefit from antiangiogenic therapy is key. “The Moore criteria, prospectively validated in the GOG 240 trial, identified that the survival benefit from bevacizumab is greatest in the moderate-risk and high-risk defined subgroups. This finding has the potential to guide oncologists in … balancing the merits of addition of bevacizumab with the risks of toxicities,” she said.
Despite the positive results, Banerjee has reservations about the reach of the drug. “The stark reality is that given the cause of cervical cancer, the need is greatest in low-income countries where 85 percent of the global cervical cancer diagnoses [and 87 percent of all cervical cancer deaths] occur. Bevacizumab is out of reach for many in these regions,” she said.
“[T]he focus needs to be on investment in and education about screening and [human papillomavirus] vaccination programmes worldwide so that palliative treatment of metastatic or recurrent cervical cancer becomes a situation of the past,” said Banerjee.