A major personalized medicine initiative at The University of Texas? M.D. Anderson Cancer Center found that matching patients with advanced cancer in Phase I clinical trials with targeted drugs on the basis of the molecular profiles of the patients? tumors resulted in higher response rates and longer survival and time to treatment failure (TTF) compared to treating patients without molecular matching.

In patients who had tumor molecular aberrations matched to specific therapies, the length of time before their treatment stopped working (TTF) was also longer compared to their prior therapies. The findings could lead to a new model for conducting Phase I clinical trials and suggest that a comparable personalized medicine approach that matches tumor molecular aberrations with appropriate targeted therapies may be feasible and lead to improved outcomes in patients with advanced cancer.

?An improving ability to perform tumor molecular analysis, coupled with the development of targeted therapies, has led to an increasing interest in a personalized medicine approach,? said lead author Apostolia-Maria Tsimberidou, MD, PhD, Associate Professor in the Department of Investigational Cancer Therapeutics at M.D. Anderson Cancer Center in Houston.

Improved clinical outcomes
?This is an innovative program that could be used as a model not only for Phase I clinical trials, but also for Phase II and Phase III trials. This therapeutic strategy should eventually be used for the treatment of every patient with cancer when identification of tumor molecular aberrations will be feasible in all patients. We have demonstrated on a large scale that this personalized medicine approach is associated with improved clinical outcomes.

Trial design
Carefully designed Phase I and randomized Phase II clinical trials that enroll a select group of patients with tumors that have the molecular abnormalities that are targeted by a promising experimental agent are a promising new and less expensive approach to drug development.?

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In the study, investigators performed molecular analyses on tumors of 1,144 patients with advanced cancer who had a median of four previous therapies, identifying one or more molecular aberrations in 460 (40.2%) patients. Patients were treated with a variety of drugs targeting molecular aberrations in genes such as PIK3CA, mTOR, BRAF, MEK, KIT, EGFR, and RET. The allocation of patients to investigational treatment varied over time according to protocol availability and eligibility criteria, the patient?s prior response to therapy, potential toxicity, insurance coverage, and patient preference or physician choice.

Researchers found that when patients were assigned targeted drugs that matched one of their tumor?s genetic aberrations, they experienced improved survival, as well as stronger and longer-lasting treatment benefits.

Median survival was 13.4 months for patients with one molecular aberration treated with matched targeted therapy, compared to 9.0 months for those patients whose treatment was not matched to their molecular aberrations.

Duration of treatment benefit
The researchers found that the median time to treatment failure in 175 patients with one molecular aberration who were treated with a matched therapy was 5.2 months, compared to 2.2 months for individuals without a matched therapy. Additionally, they found matched therapies provided a longer lasting benefit than those patients? prior chemotherapy regimens (median of 3.1 months).

Overall response rates
For patients with one identified molecular aberration, 27% had either a complete response or partial response with a matched therapy versus 5% for patients who did not receive matched therapy. In addition, stable disease for longer than 6 months was noted in 23% of patients treated with matched therapy versus 10% of those treated without matched therapy.

For more information:
Study authors: Tsimberidou AM, Iskander NG, Hong DS, Wheler JJ, Fu S, et al
Abstract title: Personalized medicine in a phase I clinical trials program: The M. D. Anderson Cancer Center initiative.
Friday June 3, 3:00 PM CDT Houston, TX E354b
Abstract: # CRA2500

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