Endometrial Cancer Update: The move toward personalized cancer care

• chemotherapy-naïve women, with no more than one prior hormonal treatment (n = 33)
• chemotherapy-treated women (n = 27).

Temsirolimus was given weekly in 4-week cycles at an intravenous (IV) dose of 25 mg over 30 minutes.

The drug elicited a response regardless of the histologic type of cancer. That response was more pronounced in chemotherapy-naïve women and not limited to patients with PTEN loss. In the chemotherapy-naïve group, four women (14%) had a partial response, 20 (69%) had stable disease, and five (18%) had progressive disease. Median PFS was 7.33 months (95% confidence interval [CI], 3.61–9.86), compared with 3.25 months (95% CI, 1.97–3.84) in chemotherapy-treated women. Among chemotherapy-treated women, one (4%) had a partial response and 12 (48%) had stable disease.

An angiogenesis inhibitor alone was well tolerated
VEGF is the principal growth factor responsible for angiogenesis, initiating the process of neovascularization. Bevacizumab is a humanized monoclonal antibody that binds to circulating VEGF-A, stimulating clinical effects in multiple tumor types, including persistent or recurrent ovarian and cervical cancers.

Aghajanian and colleagues conducted a Phase II trial of single-agent bevacizumab in women with recurrent or persistent endometrial cancer to assess the drug’s activity and tolerability. Eligible patients had histologic confirmation by central pathology review, recurrent or persistent disease after one or two cytotoxic regimens, and a Gynecologic Oncology Group performance score of 2 or lower. They received IV bevacizumab 15 mg/kg every 3 weeks until the disease progressed or toxicity became prohibitive. Fifty-two women participated.

Seven women (13.5%) experienced a clinical response (one complete response and six partial responses), and 21 (40%) had PFS of at least 6 months. Median PFS and overall survival were 4.2 and 10.5 months, respectively.

Combined with temsirolimus, bevacizumab increased overall survival

Alvarez and colleagues conducted a Phase II trial of combination bevacizumab and temsirolimus in women with recurrent or persistent endometrial carcinoma. Forty-nine patients participated.

These women had undergone earlier treatment with one (82%) or two (18%) chemotherapy regimens and radiation (41%). Median PFS and overall survival were 5.6 and 16.9 months, respectively. Toxicity was significant, with 38.8% of women withdrawn from the study due to toxicity.

What this evidence means for practice
Given the findings regarding temsirolimus and bevacizumab as single agents, their use in combination was expected to produce a robust effect. The 6-month PFS rate is similar for all three regimens, but for overall survival, combination therapy had a 6.4-month advantage over bevacizumab alone.

Given the significant toxicity associated with the combination of bevacizumab and temsirolimus, further study is needed to develop biomarkers to predict response and toxicity. Other areas meriting future research include optimal timing of angiogenesis and mTOR pathway inhibitors, different combinations of agents, and the identification, through genomic analysis, of patient populations most likely to benefit from these drugs with minimal toxicity.

The studies presented here show promise in the area of genomics and represent the beginning of our movement toward personalized cancer care.

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