Abstract 1287: Profile-related evidence to determine individualized cancer therapy (PREDICT): Preliminary results of the Personalized Phase I Clinical Trials program at MD Anderson Cancer Center

Abstract

Abstract Introduction: To assess the outcomes of molecularly targeted therapy, we analyzed the results of mutational analyses in patients seen in our Phase I clinic and assessed patient survival by the number of mutations in patients treated with and without matched targeted therapy. Methods: Mutational analysis was mostly performed in the CLIA-certified pathology laboratory. DNA was extracted from microdissected paraffin-embedded tumor samples. The following genes were analyzed: PIK3CA (exon 9: codons 532-554; exon 20: codons 1011-1062); BRAF (exon 15: codons 595 to 600); KRAS and NRAS (codons 12, 13, 61); EGFR (exons 18 to 21, kinase domain); KIT (exons 9, 11, 13, 17); and RET (exon 10: codons 609, 611, 618, 620; exon 11: codon 634; exon 16: codon 918). The loss of the tumor suppressor nuclear protein (PTEN) was determined by immunohistochemistry. The allocation of patients to clinical trials varied according to protocol availability; eligibility; patient's prior response to therapy, toxicity and preference; and physician's choice. Patients whose tumor had a mutation were preferably treated with a matched targeted agent. Survival was compared between patients treated with and without matched targeted therapy. Results. Of 849 patients who had tissue available, 354 (41.7%) had ≥ 1 mutation (1, n=313; 2, n=38; 3, n=3) (Table 1). The median survival of patients with 0 vs. 1 vs. 2-3 mutations was 9.4 vs. 11.7 vs. 7.3 months, respectively (p =0.02; Table 2). In 278 evaluable patients with 1 mutation, the 2-yr survival rates were 42% and 17% (p = 0.02) for patients treated with and without matched targeted therapy. Conclusion: In patients with 1 mutation, treatment with matched targeted therapy was associated with superior survival compared to treatment without matching. Patients with 1 mutation had longer survival than those with no or >1 mutation, perhaps because most of them were treated with a matched targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1287. doi:10.1158/1538-7445.AM2011-1287