Prospective Validation of Pooled Prognostic Factors in Women with Advanced Cervical Cancer Treated with Chemotherapy with/without Bevacizumab: NRG Oncology/GOG Study

Abstract

Purpose In the randomized phase III trial, Gynecologic Oncology Group protocol 240, the incorporation of bevacizumab with chemotherapy significantly increased overall survival (OS) in women with advanced cervical cancer. A major objective of GOG-240 was to prospectively analyze previously identified pooled clinical prognostic factors known as the Moore criteria. Experimental Design Potential negative factors included black race, performance status 1, pelvic disease, prior cisplatin, and progression-free interval <365 days. Risk categories included low-risk (0-1 factor); intermediate-risk (2-3 factors); high-risk (4-5 factors). Each test of association was conducted at the 5% level of significance. Logistic regression and survival analysis was used to determine whether factors were prognostic or could be used to guide therapy. Results For the entire population (n=452), high-risk patients had significantly worse OS (p<0.0001). The hazard ratios of death for treating with topotecan in low-risk, mid-risk, and high-risk subsets are 1.18 (95% CI 0.63-2.24), 1.11 (95% CI 0.82-1.5), and 0.84 (95% CI 0.50-1.42), respectively. The hazard ratios of death for treating with bevacizumab in low-risk, mid-risk, and high-risk subsets are 0.96 (95% CI 0.51-1.83; p=0.9087), 0.673 (95% CI 0.5-0.91; p=0.0094), and 0.536 (95% CI 0.32-0.905; p=0.0196), respectively. Conclusions This is the first prospectively validated scoring system in cervical cancer. The Moore criteria have real world clinical applicability. Toxicity concerns may justify omission of bevacizumab in some low-risk patients where survival benefit is small. The benefit to receiving bevacizumab appears to be greatest in the moderate- and high-risk subgroups (5.8 month increase in median OS).

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)

“…Importantly, the prospective validation of the Moore clinical criteria 12 in GOG 240 provides oncologists with the first scoring system in cervical cancer which can be used to estimate response and survival and potentially identify patients who are best treated without bevacizumab (e.g., a pre-irradiated patient at risk for fistula for whom the survival benefit attributable to adding bevacizumab is negligible). 17 It should be noted that the late injury of radiotherapy is microvascular and therefore preirradiated patients being considered for treatment with chemotherapy plus bevacizumab should be counseled that the risk of vascular complications may be increased.…”

Should We Cease to Perform Salvage Hysterectomy After Chemoradiation and Brachytherapy in Locally Advanced Cervical Cancer?

“…The authors concluded that the benefit of bevacizumab was greatest in the moderate (2-3 factors) and high-risk (4-5 factors) subgroups (a 5.8-month increase in median OS). However, the survival benefit was small for lowrisk patients (0-1 factor) and toxicity concerns may justify omitting bevacizumab in this case (31).…”

Prognostic models for locally advanced cervical cancer: external validation of the published models

“…The structure of both reviews has elements in common with the one presented here and with the proposal found in the Cochrane manual of systematic reviews of interventions [ 38 ]. Other works present validation analyses of prognostic models in patients with early cervical cancer [ 39 ], LACC [ 17 ], and disseminated cancer [ 40 ]. However, only an independent external validation study of 2 predictive models in patients with LACC performed in different population was published [ 24 ].…”