Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199)

- This phase II clinical trial studied the activity of temsirolimus, an mTOR inhibitor, in advanced/recurrent/metastatic cervical cancer.
- Response rates were low, however the rates of disease stability and 6 month progression free survival rates were notable.
- Molecular correlates of the AKT/mTOR pathway correlating with disease stability were not identified using archival tumour tissue.

ObjectiveHPV infection has been associated with deregulation of the PI3K-Akt-mTOR pathway in invasive cervical carcinomas. This 2-stage phase II study assessed the activity of the mTOR inhibitor, temsirolimus, in patients with measurable metastatic and/or locally advanced, recurrent carcinoma of the cervix.MethodsTemsirolimus 25 mg i.v. was administered weekly in 4 week cycles. One response among the first 18 patients was required to proceed to the second stage of accrual. Correlative molecular studies were performed on archival tumor tissue.ResultsThirty-eight patients were enrolled. Thirty-seven patients were evaluable for toxicity and 33 for response. One patient experienced a partial response (3.0%). Nineteen patients had stable disease (57.6%) [median duration 6.5 months (range 2.4-12.0 mo)]. The 6-month progression free survival rate was 28% (95% CI: 14-43%). The median progression free survival was 3.52 months [95% CI (1.81-4.70)]. Adverse effects were mild-moderate in most cases and similar to other temsirolimus studies. No toxicity > grade 3 was observed. Assessment of PTEN and PIK3CA by IHC, copy number analyses and PTEN promoter methylation status did not reveal subsets associated with disease stability.ConclusionSingle agent temsirolimus has modest activity in cervical carcinoma with about two-thirds of patients exhibiting stable disease. Molecular markers for treatment benefit remain to be identified.