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Phase 1 trial shows promise in personalized therapy approach

BY ELIZABETH WHITTINGTON
PUBLISHED SATURDAY, JUNE 4, 2011
At each ASCO annual meeting, we hear that we are moving a little further toward personalized medicine, which means looking at more than just where the tumor originated lung cancer, breast cancer, etc -- but actually targeting what drives the tumor.

Friday afternoon, Apostolia Tsimberidou, a M.D. Anderson Cancer Center researcher and professor in the department of Investigational Cancer Therapeutics, described an exploratory phase 1 trial where they took samples of tumor tissue from 1,144 patients and looked for specific tumor markers, such as BRAF, EGFR and KRAS. In more than a third of patients, researchers were able to identify at least one mutation.

Using the molecular profiling information, researchers chose treatment not based on tumor location, but mutation status. For example, if a breast tumor was identified as EGFR-positive, the patient may be treated with the lung cancer drug Tarceva (erlotinib) because it targets the EGFR mutation. It should be pointed out that the trial was only examining the concept of targeting tumors based on mutations--not testing specific drugs to specific cancers.

If this type of trial sounds like the lung cancer BATTLE trial where lung tumors were treated based on molecular markers, it's because the researchers at M.D. Anderson were inspired by the idea of the trial.

The BATTLE (Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination) trial is unique in that researchers are testing several drugs, each designed to target a particular cancer pathway. Patients with advanced non-small cell lung cancer were assigned a drug, and their tumors were assayed for certain biomarkers. As the researchers evaluated what appeared to work, they changed strategy: Patients with known tumor biomarkers were treated with the drug that had worked best for earlier patients with similar biomarkers.

It's worth noting that the M.D. Anderson phase 1 trial was not randomized (randomly assigning patients to a matched therapy or non-matched therapy), but instead, researchers compared response rates from the matched therapy to a response from a prior therapy. Survival and the time to treatment failure improved when patients were given treatment according to the tumor's aberrations, or genetic mutations.

The trial examined many different tumor types, including melanoma, thyroid, endometrial, lung, colorectal, breast and pancreatic cancers. Many of these patients were referred to the phase 1 trial because their cancer was deemed "incurable." Some had up to five different prior therapies, and had few treatment options left.

While the trial produced some interesting ideas on how to test new drugs and treat patients, it must also be recognized that most patients in the trial did not have an identifiable gene mutation, which means we still have much to learn. Don't be surprised to see more trials in the near future focus more on molecular profiling than tumor location.

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