Journal article
Custom (Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies) trial
Journal of clinical oncology, v 31(15_suppl), pp 7513-7513
20 May 2013
Abstract
Abstract only 7513 Background: CUSTOM is the first completed prospective clinical trial using molecular selection for treatment assignments into multiple targeted therapy arms and in multiple cancer histological subtypes concurrently. Methods: All patients with advanced NSCLC, SCLC or TM were eligible to participate in the study. Oncogenic mutations, amplifications or translocations in 12 genes detected in CLIA-certified laboratories were used to assign patients to 1 of 5 biomarker/treatment groups per histological subtype: EGFR mutations/erlotinib; KRAS, NRAS, HRAS or BRAF mutations/AZD6244; PIK3CA, AKT or PTEN mutations/MK2206; ERBB2 mutations or amplifications/lapatinib; and KIT or PDGFRA mutations/sunitinib; or to standard-of-care therapy. For each arm, the study was conducted as an optimal two-stage phase II trial in favor of a response rate of 40% or more. Results: 668 patients were enrolled at two academic institutions. The most frequent genetic alterations in NSCLC were KRAS and EGFR mutations (25.2 and 19.7% respectively), ALK rearrangements 7.8%, HER2 amplifications 2.7% and mutations in PIK3CA 2.5%, BRAF 1.9%, HRAS 1.5%, ERBB2 1.7%, AKT1 0.4%, and NRAS 0.7%. PTEN mutation analysis was only feasible in 13 patients with NSCLC of which 3 were positive (23%). The most frequent genetic alterations in SCLC were mutations in PIK3CA 6.5%, ERBB2 amplifications 5.3% and mutations in HRAS 3.4%, AKT1 2.2%, BRAF 2% and KRAS 2%. The most frequent genetic alterations in TMs were HER2 amplifications 7.7% and mutations in HRAS 4.7%, PIK3CA 1.4% and EGFR 1.4%. Only 6.2% (n=42) of patients met criteria for enrollment into the treatment arms of the study. Efficacy analyses including response rates will be presented. Conclusions: CUSTOM is the first completed prospective clinical trial demonstrating the feasibility of conducting efficacy analyses of multiple biomarker-matched therapies in multiple cancer histological subtypes concurrently. CUSTOM is also the largest prospective molecular profiling study of patients with SCLC and TMs. Clinical trial information: NCT01306045.
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Details
- Title
- Custom (Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies) trial
- Creators
- Giuseppe Giaccone - National Cancer InstituteAriel Lopez-Chavez - Oregon Health & Science UniversityAnish Thomas - National Cancer InstituteArun Rajan - National Cancer InstituteMark Raffeld - Molecular Diagnostics Core Laboratory, CCR, NCI, NIH, Bethesda, MDRegan M. Duffy - Oregon Health & Science UniversityBetsy Morrow - National Cancer InstituteYisong Wang - National Cancer InstituteCorey Allan Carter - National Cancer InstituteUdayan Guha - National Cancer InstituteKeith Killian - National Cancer InstituteChristopher Y. Lau - National Cancer InstituteZied Abdullaev - National Cancer InstituteLiqiang Xi - Molecular Diagnostics Core Laboratory, CCR, NCI, NIH, Bethesda, MDSvetlana Pack - National Cancer InstitutePaul S. Meltzer - National Cancer InstituteChristopher L. Corless - Oregon Health & Science UniversityCarol Beadling - Oregon Health & Science UniversityAndrea Warrick - Oregon Health & Science UniversityEva Szabo - National Cancer Institute
- Publication Details
- Journal of clinical oncology, v 31(15_suppl), pp 7513-7513
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Other Identifier
- 991022059862404721