Abstract P2-08-13: Integrating multiplex and next generation sequencing (NGS) platforms in routine molecular profiling of metastatic breast cancer (MBC) patients (pts): Trends for enrollment in genotype-directed clinical trials (GDTs)
Authors: M Oliveira, R Dienstmann, M Bellet, JM Pérez-Garcia, P Gómez, E Muñoz-Couselo, M Vidal, V Ortega, E Zamora, J Soberino, A Meire, P Nuciforo, A Vivancos, J Cortés, C Saura
Journal: Cancer Research (2016)

Abstract Background/aims: Multiplex or NGS platforms increase the number of mutations (mut) detected in tumor samples respect to single-gene sequencing techniques. We aimed to assess the actionable molecular alteration (ActMA) detection rate and the enrollment in GDTs derived from the integration of these platforms in routine molecular profiling of MBC pts, in addition to FISH and IHC techniques already in use. Methods: Consecutive MBC pts screened for gene mut by Sequenom (Seq) or AmpliconSeq (ASeq) were identified. Data on FGFR1 amplification (amp), PTEN IHC, and enrollment in GDTs were collected. ActMA: any mut, PTENnull (IHC score=0), or FGFR1/HER2amp for which a matched targeted drug might be available. Targeted therapy: treatment with PI3K/mTOR, novel anti-HER2, FGFR, or AKT inhibitors (inh) irrespective of having ActMA. GDT: treatment matched to ActMA. Results: From Oct2010-Apr2015, 260 pts screened (Seq 207, ASeq 53). IHC subtype: HR+/HER2- (LUM) 65%, HER2+ 13.5%, TN 19.6%, unk 1.9%. 84 samples from a metastatic site (32.3%). ActMA / n (%)LUMHER2+TNP value (Fisher's exact test)TotalTP53*11 (31.4)1 (50)9 (52.9)0.3421 (38.9)PIK3CA44 (26)10 (28.6)4 (7.8)0.158 (22.7)FGFR1amp21 (17.4)1 (5.3)6 (16.7)0.4728 (15.9)PTENnull12 (9.3)2 (7.7)9 (25)0.0323 (12)AKT110 (5.9)1 (2.9)-0.1511 (4.3)ERBB23 (1.8)---3 (1.2)EGFR1 (0.6)-2 (4.1)-3 (1.2)ESR1*1 (3)---1 (2)KRAS2 (1.2)---2 (0.8)Denominators vary according to platform. *Amplicon only Proportion of PIK3CAmut was similar irrespective of the site of analysis (primary 25.5%, metastasis 21.4%; P=0.63) and platform (Seq 22.2%, ASeq 24.5%, P=0.72). ASeq detected more mutations in actionable genes than Seq (36% vs. 29%, P=0.01). At least 1 ActMA (range 0-3) was found in 53.5% of pts, with non-significant differences in HER2- subtypes (LUM 48.5% vs. TN 39.2%, P=0.32). Subtype* / ActMA n (%)≥10123All139 (53.5)121 (46.5)111 (42.7)25 (9.6)3 (1.2)LUM82 (48.5)87 (51.5)71 (42)9 (5.3)2 (1.2)HER2+35 (100)-22 (62.9)12 (34.3)1 (28)TN20 (39.2)31 (60.8)16 (31.4)4 (7.8)-*5 pts with unk subtype not shown Pts with ≥2 ActMA (excluding HER2amp): 11 LUM (interestingly, 3 pts with PIK3CAmut+FGFR1amp), 1 HER2+, and 4 TN. Overall, 56% of pts received ≥1 targeted therapy (range 0-4). From the 139 pts with ≥1 potential ActMA (including HER2amp if treated with a novel anti-HER2), 61.8% received a targeted therapy and 42.4% were enrolled in a GDT: PI3K/mTOR inhibitor (inh) 54 (64.3%), novel anti-HER2 16 (19.1%), FGFR inh 8 (9.5%), AKT inh 6 (7.1%). Of the 121 pts that did not have potentially ActMA, 50% received a targeted therapy. The OR for receiving targeted therapy if ActMA was present was 1.59 (95%CI 0.94-2.70, P=0.08). Conclusion: Integration of multiplex and NGS platforms in routine molecular profiling of MBC pts yields a detection rate of ActMA &amp;gt;50%, which translates into higher probability of receiving a targeted agent and enrollment in a GDT. This suggests that physicians are pushing towards matched targeted therapies for pts that participate in molecular screening programs and have ActMA. Results on the outcome of these pts will be presented. Citation Format: Oliveira M, Dienstmann R, Bellet M, Pérez-Garcia JM, Gómez P, Muñoz-Couselo E, Vidal M, Ortega V, Zamora E, Soberino J, Meire A, Nuciforo P, Vivancos A, Cortés J, Saura C. Integrating multiplex and next generation sequencing (NGS) platforms in routine molecular profiling of metastatic breast cancer (MBC) patients (pts): Trends for enrollment in genotype-directed clinical trials (GDTs). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-13.