Abstract C48: BIP (Bergonie Institute profiling) program: Fighting cancer by matching molecular alterations and drugs in early phase trials

Abstract

Abstract Background: BIP is an institution-wide permanent screening program started in 2014 to identify patients (pts) referred to Institut Bergonié (Bordeaux, France) with somatic alterations that can be matched to targeted therapies in early phase clinical trials. Methods: Pts with advanced solid tumors and with ECOG performance status ≤ 2 were eligible. Tumor DNA was isolated from a FFPE archived sample when available or from a fresh tumor biopsy. DNA analysis was performed by next generation sequencing (NGS) using a panel of up to 287 genes and by comparative genomic hybridization (CGH). Results for each patient were discussed during a weekly multidsicplinary molecular tumor board in order to assess the eligibility of the patient to early phase clinical trials. Results: From Jan 1 2014 to June 30 2015, 542 pts were enrolled with median 2 prior treatments for advanced disease (range 0-9). The main tumor types were: lung (19.2%), colorectal (16.2%), breast (13.3%), ovarian (11%), and sarcomas (10%). Median age was 61 years (range 18-84). In 28 cases (5%) molecular analysis failed mainly because of insufficient tissue. The median time from first referral to reporting was 9 weeks (range 1-36). The 20 genes most frequently altered were TP53, CDKN2A,PTEN, CDKN2B, PIK3CA, MYC, ARID1A, KRAS, RB1, EGFR, ERBB2, FGFR1, APC,RICTOR,ZNF703,ATM,BRAF,NF1,FGFR3 and CCND1. Among the patients included between Jan 1 2014 and January 31 2015 (n = 286), 176 patients (68%) of patients had at least one genetic alteration that was considered actionable by the molecular tumor board. 85 patients (29.7%) were included in a clinical trial with a median delay of 17 weeks between first referral and date of treatment onset. The treatment was matched with the tumor profile in 49 cases (17%). The main reasons for non-inclusion in a clinical trial despite the identification of an actionable mutation were: non progressive disease on the current line of treatment (31.5%), general status deterioration (26%), death (13%), clinical trial not available (13%), screening failure (6.5%), lost of follow-up (5.5%), and patient refusal (4.5%). 79 patients were evaluable for response according to RECIST 1.1. The disease control rate (objective response + stable disease) was 47% for patients included in clinical trials matched with the tumor profile versus 53% (p = 0.9) for the group of patients included in other clinical trials The median progression-free survival was 3.6 months (95 CI 1.8-5.3) versus 3.6 months (95 CI 0.9-6.3) (p = 0.5). Conclusions: Extensive molecular profiling by using high-throughput techniques is feasible in routine practice, allow identification of actionable mutations in the majority of cases and can be used to enroll patients in early phase trials matched to their tumor genotype. Citation Format: MAUD TOULMONDE, THOMAS GRELLETY, CELINE AUZANNEAU, YEC'HAN LAIZET, KEVIN TRAN, ANNE FLOQUET, DELPHINE GARBAY, JACQUES ROBERT, ISABELLE HOSTEIN, ISABELLE SOUBEYRAN, ANTOINE ITALIANO. BIP (Bergonie Institute profiling) program: Fighting cancer by matching molecular alterations and drugs in early phase trials. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C48.