Targeted therapy increased response rates, survival in patients with molecular abnormalities

2011 ASCO Annual Meeting

CHICAGO — Matching tumor molecular aberrations with appropriate targeted therapies resulted in higher response rates, and longer survival and time-to-treatment failure compared with treating patients without molecular matching, according to researchers from The University of Texas M.D. Anderson Cancer Center.

“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,” Apostolia-Maria Tsimberidou, MD, PhD, associate professor in the department of Investigational Cancer Therapeutics at M.D. Anderson Cancer Center, said in a press release. “This is an innovative program that could be used as a model not only for phase 1 clinical trials, but also for phase 2 and phase 3 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.”

The researchers analyzed tissue for molecular aberrations, including PIK3CA, BRAF, EGFR and PTEN (CLIA), from 1,144 patients referred for treatment on phase-1 clinical trials. Nearly half of all patients had one to four aberrations (40.2%) and 33.1% had one aberration.

According to their findings, survival improved among patients assigned to targeted therapy that matched one of their tumor’s aberrations, with treatment benefits that were stronger and lasted longer than prior systemic therapy.

Among patients with one aberration, median survival was 13.4 months compared with 9.0 months among those whose treatment was not matched to their molecular aberrations. In addition, the median time to treatment failure in 175 patients with one aberration who were treated with matched therapy was 5.2 months compared with 2.2 months for those not treated with matched therapy (P<.0001). In addition, matched therapy resulted in longer treatment benefit compared with prior chemotherapy regimens (median of 3.1 months).

Complete or partial response occurred among 27% of patients with one aberration who were treated with matched therapy compared with 5% of those who did not receive matched therapy (P<.0001). Additionally, 23% of patients who received matched therapy had stable disease for longer than 6 months (23%) compared with those who did not receive matched therapy (10%).

“We have demonstrated, on a large scale, that this personalized medicine approach is associated with improved clinical outcomes,” Tsimberidou said in the release. “Carefully designed phase 1 and randomized phase 2 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.” – by Stacey L. Fisher

Disclosure: Dr. Tsimberidou reports a consultant or advisory role for Cephalon, Sanofi.

For more information:

• Tsimberidou AM. CRA 2500. Presented at: 2011 ASCO Annual Meeting; Chicago; June 3-7, 2011.

To me, what this study demonstrates is a couple of things. One is that, customarily in phase 1 clinical trials and as I understand it the treatment given to these patients were often in the context of phase 1 clinical trials, it has been unusual over many years for phase 1 trials to see significant numbers of patients who actually benefit from the treatment. Historically it’s been in the 5% to10% range. I think what this study illustrates is if you actually have a way of identifying which therapy is likely to work in a patients you can substantially increase the likelihood of benefit for a patient even with advanced cancer, even in a phase 1 trial. Secondly, I would think that this type of approach is going to substantially accelerate the rate of development of these new drugs because not only will it be possible, in a phase 1 trial, to learn about their toxicity and pharmacokinetics and things that we customarily learn about in phase 1 trials, but now we’ll actually be able to get a better sense of what their activity is in treating patients, which is something that oftentimes has had to be delayed until phase 2 or later stage trials. This is certainly not a perfect approach. Obviously, not every patient had a specimen available, not every patient had a “actionable” aberration and even when they did the treatment didn’t always work; the response rate was only about 25%. So even with this approach, 75% of the time, the tumor did not shrink. I’m sure there are many reasons for that that Dr. Tsimberidou and her colleagues can comment on. That said, I think that this still represents a substantial improvement in the way we can do drug development in patients with cancer these days.

- Richard Schilsky, MD

Professor of Medicine and Section Chief of Hematology/Oncology,
University of Chicago Medical Center

Disclosure: Dr. Schilsky is a member of SAB of Foundation Medicine, and a member on the Board of Directors of Universal Oncology

Follow HemOncToday.com on Twitter.