CHICAGO (FRONTLINE MEDICAL NEWS) – Circulating tumor cells are a prognostic biomarker for overall survival in women with advanced cervical cancer who are receiving chemotherapy with or without bevacizumab, according to an analysis of the Gynecologic Oncology Group’s 240 trial.

The risk of death among patients given cisplatin-paclitaxel plus bevacizumab was reduced by 10% for those who had a higher pretreatment level of circulating tumor cells (CTCs) and by 13% for those who had a greater treatment-related decline in CTCs, Dr. Krishnansu S. Tewari reported at the annual meeting of the Society of Gynecologic Oncology.

“We can predict that leaky vasculature resulting from tumor angiogenesis may permit systemic distribution of CTCs through intratumoral vascular shunting, and the vulnerability to anti-angiogenesis therapies may be due to this increased vascularization,” said Dr. Tewari of UC Irvine Health in Orange, Calif.

In comments provided by e-mail, session comoderator Dr. Charles N. Landen Jr. of the University of Virginia, Charlottesville, said that the study is important in that it demonstrates the feasibility of using CTCs as a biomarker in this setting, but its results are not practice changing.

“If you had a decrease in CTCs, you were more likely to have a good response to therapy. However, this was not any better at detecting response than conventional methods such as a CT scan,” he explained.

Giving some background to the research, Dr. Tewari said that “it’s difficult to monitor response in patients with advanced cervical cancer. Doing imaging studies after every two cycles is expensive, and there are no validated serum tumor markers in this disease. In addition, tumor is not often accessible for interrogation to help guide subsequent therapy when patients ultimately progress on anti-VEGF [vascular endothelial growth factor] therapy. Finally, predictive biomarkers are lacking in advanced cervical cancer.”

“CTCs can be seen as minimally invasive liquid biopsies, and their presence in breast cancer, prostate cancer, and non–small cell lung cancer has been correlated with survival,” he noted. “However, all three of those solid tumors are known to spread hematogenously. While hematogenous spread can occur in cervical cancer, it is felt to be rare.”

The phase III trial enrolled women with recurrent, persistent, or metastatic cervical cancer and tested the addition of bevacizumab (Avastin, manufactured by Genentech/Roche) to doublet chemotherapy (cisplatin-paclitaxel or topotecan-paclitaxel) given on 21-day cycles. Main results showed a significant gain in overall survival from the addition of bevacizumab (N. Engl. J. Med. 2014;370:734-43), leading to regulatory approval of combination therapy in the United States and elsewhere.

The new analysis focused on the 174 women (39%) in the trial who had 8.5 mL of whole blood collected for CTC measurement before starting the first cycle of therapy and, in most cases, again 36 days after the first cycle.

The investigators were able to identify CTCs for 97% of patients in the pretreatment sample and for 81% in the post-treatment sample, Dr. Tewari noted.

Results showed that the median CTC count in the sample fell from seven cells pretreatment to four cells post-treatment (P < .0001). Of note, there was no correlation with the response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors).

Patients with high (above-median) pretreatment levels of CTCs had significantly better median progression-free survival with bevacizumab than without it (10.8 vs. 6.9 months; hazard ratio [HR], 0.59). In contrast, there was no significant benefit for patients with low (below-median) pretreatment levels of CTCs (7.3 and 6.2 months).

Among patients given cisplatin-paclitaxel plus bevacizumab, the higher the pretreatment CTC level, the lower the risk of death (HR, 0.90). Among patients given cisplatin-paclitaxel overall, the higher the post-treatment CTC level, the greater the risk of death (HR, 1.12), Dr. Tewari reported.

Finally, the greater the decline in CTCs from before to after treatment in patients given cisplatin-paclitaxel plus bevacizumab, the lower the risk of death (HR, 0.87), he said.

Dr. Tewari disclosed that he is a consultant to Genentech/Roche, Advaxis, and Caris Life Sciences; receives honoraria/reimbursement or grants from Genentech/Roche; and performs research for Caris Life Sciences.


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