Personalized Medicine Comes of Age at ASCO 2011

June 2011, Vol 2, No 3 -

Chicago, IL—Personalized medicine was the subject of the first press conference held at ASCO 2011 and the topic of one of the scientific sessions.

Large-Scale Evidence for Benefits of Targeted Therapies
Apostolia M. Tsimberidou, MD, PhD, Associate Professor, Department of Investigational Cancer Thera – peutics, Division of Cancer Medicine, M. D. Anderson Cancer Center, Houston, headed a phase 1 clinical trial based on the hypothesis that tumor molecular analysis and use of targeted therapies to counteract the effects of specific mutations would improve patient outcomes.

In this exploratory, nonrandomized study, 1114 patients underwent molecular analysis; of these, 460 patients were identified with between 1 and 4 known oncogenic mutations, including KRAS (19%), BRAF (19%), and PIK3CA (10%). These patients were then matched to available and/or investigatory targeted therapies, and treatment outcomes were compared with nontargeted therapy (ie, standard of care) controls.

Among patients with 1 aberration, the results were striking—the overall response rate was 27% in the targeted therapy group versus 5% in the standard of care group (P <.01). The treatment superiority was evident by an increased disease stabilization and time to treatment failure (TTF).

“There was a median increase of 3 months in TTF, which was also associated with median increased survival of 13.4 versus 9 months,” said Dr Tsimberidou. “We have demonstrated on a large scale that this personalized medicine approach is associated with improved clinical outcomes.”

Striking Activity with Crizotinib
Results from an ongoing, open-label, phase 1 study further highlights the progress made with personalized medicine. The study drug was crizotinib, which targets the pathway of the anaplastic lymphoma kinase (ALK) gene mutation, a key oncogenic driver in non–small-cell lung cancer (NSCLC). “ALK rearrangements in lung cancer were first described in 2007 and occur in between 3% and 5% of all NSCLC cases,” said D. Ross Camidge, MD, PhD, Associate Professor, Division of Medical Oncology, University of Colorado, Denver.

The first human study of crizotinib was launched in 2006, but after the discovery of the ALK-NSCLC connection, the study was amended to screen for patients who were positive for ALK mutations. Dr Camidge presented results from 116 patients with ALK-positive NSCLC who were treated with crizotinib 250 mg twice daily in 28-day cycles.

At a median follow-up of 11 months, the overall response rate was an impressive 61% in this heavily pretreated patient population. The responses were rapid (median 8 weeks), and the preliminary median progression-free survival period was 10 months.

“The striking activity of crizotinib in ALK-positive lung cancer was apparent very early in clinical development,” said Dr Camidge. “This demonstrates that robust efficacy signals may be revealed, even within small cohorts where the population is molecularly uniform.”

Treatment-related adverse events were mild, mainly gastrointestinal, manifested early, and diminished as treatment continued.

Phase 3 clinical trials have been initiated, and given the robust nature of these results, the drug manufacturer is seeking accelerated approval from the US Food and Drug Administration in conjunction with these trials.