Bevacizumab Plus Chemotherapy Prolongs PFS in Endometrial Cancer With p53 Null Status

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p53 mutational status may be a viable strategy upon which to base the course of therapy.
p53 mutational status may be a viable strategy upon which to base the course of therapy.
The following article features coverage from the Society of Gynecologic Oncology 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

Women with endometrial cancer with null p53 status may respond to bevacizumab plus chemotherapy, according to an oral presentation at the 2018 Society of Gynecologic Oncology Annual Meeting on Women's Cancer in New Orleans.1

p53 mutational status may be a viable strategy upon which to base the course of therapy; previous studies demonstrated that molecular inhibition and chemotherapy may be effective for this patient population.

For the phase 2 GOG/NRG Study 86P, researchers randomly assigned 250 patients to 1 of 3 treatment arms: bevacizumab plus paclitaxel and carboplatin, temsirolimus plus paclitaxel and carboplatin, or ixabepilone, carboplatin, and bevacizumab. Investigators performed DNA sequencing of TP53 and immunohistochemistry for p53 on 250 patients to determine their p53 status (wildtype, loss of function (LOF)/null, gain of function (GOF)/oncogenic), and to evaluate the relationship between p53 status and progression-free survival (PFS).

Patients with p53 null status who received bevacizumab plus chemotherapy had a prolongation in PFS compared with temsirolimus plus chemotherapy. Patients treated with bevacizumab and chemotherapy with the null mutation had a PFS of 19.6 months vs 12.2 months with the p53 wildtype vs 10.6 months with an oncogenic mutation.

The authors said that “the molecular mechanism of synthetic lethality was found to result from the ability of agents such as bevacizumab, which block signaling downstream of tyrosine kinases, to abrogate cell cycle checkpoints in the absence of p53. This causes the premature entry of cancer cells into vulnerable phases of the cycle where chemotherapeutic agents are most active.”

Read more of Cancer Therapy Advisor's coverage of the Society of Gynecologic Oncology 2018 meeting by visiting the conference page.

Reference

  1. Mallen AR, Filiaci VL, Levine DA, et al. Evidence for synthetic lethality between bevacizumab and chemotherapy in advanced, p53 null endometrial cancers. Oral presentation at: 2018 Society of Gynecologic Oncology Annual Meeting on Women's Cancer; March 24-27, 2018; New Orleans, LA.

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