Abstract 2601: Clinical outcomes of pts with advanced solid tumors treated according to NGS guided-therapy in a Brazilian cancer center
Authors: Costa Marcos Andre , Santos Marcelo , Abramoff Roberto , D'alpino Renata , Teixeira Carlos , Kann Ariel , Tabacof Jacques , Younes Riad 
Published: August 2018

Abstract
Introduction: Next Generation Sequencing (NGS) is a key tool since it unreveals genetic alterations (GA) with potential for targeted-therapy, frequently, not detected for conventional methods done previously. Nevertheless, avaiability of these drugs is a major concern and, additionally, oncologists are challenged to deal with such a huge amount of findings whose clinical significance and sensibility to those drugs are, many times, uncertain. Is broadly unknown, except for isolated initiatives, the correlated clinical outcomes of targeted-therapy guided by NGS.
Methods: In this retrospective study, we describe clinical outcomes of 34 pts with advanced solid tumors (tu) treated in a single Cancer Center in Brazil according to therapies guided by NGS. All tests were performed using Illumina HiSeqs of Foundation Medicine (FM). The f/u was obtained from our electronic charts.
Results: From apr/14 to oct/17, 34 pts were identified, 13M/21F, mean 58y/o. Histologies were: 7 NSCLC, 10 mCRC, 3 pancreatic, 3 breast and 11 varied. In 26 / 34 pts (76%), druggable GA were identified and 17 (50%) were treated with NGS-guided therapies - 14 with TKi and 3 with immunotherapy (imm). Importantly, 8/ 17 pts (47%) experienced clinical benefit (DE, PR, CR) by RECIST 1.1 (1 melanoma, 1 colon, 6 lung adeno). Seven (41%) had PD in the first control in 4-8w (mCRC treated with cobimetinib because of TP53 G12D; mCRC-trastuzumab-HER2 R678Q; breast-olaparibe-BRCA-2 T431fs*20; breast-EVE-PIK3CA E545K; endometrium-EVE-PIK3CA C604R/PIK3CA E81K and PTEN R233*/PTEN S229; mCRC-trastuzumab+lapatinib-HER2 amplification V777L; HCC-EVE-IKBKE amplification and PTEN loss exon 2-9), 1 had just started the therapy (BRCA-2 mutated pancreatic adeno with olaparib) and 1 died before restaging (HER2-mut mCRC treated with chemo+trastuzumab). The DoR was better in those with anti-ALK (3 pts, 18 mo) and anti-EGFR (1 pt, 6 mo ongoing response) and in those with TMB-I/high treated with imm (1 melanoma with TMB27 and 2 lung adeno with TMB 18 and 8). Amongst the 10 pts with evaluable TMB values, 6 were TMB-I/high and, in those, was found a high frequency of mutations: mean of 7). Curiously, 1 pt with mCRC with Kras G12V mutation treated with Trametinib, according to FM recommendations, experienced SD for 12 mo. Finally, 7 pts had samples tested by local companies using other methods (IHC, FISH, PCR) and in 5 (14% of all 34) it did not identified the GA observed by NGS.
Conclusion: NGS identified a significant amount of GA otherwise not detected by conventional tools, changed management and resulted in improved clinical benefit, especially for those with lung adeno treated by anti-ALK/EGFR and those with TMB-I/high treated by imm. Addionally, this study suggests that tu with higher amount of GA in NGS are prone to harbor TMB-I/high and also confirms the low responsiveness of solid tumors to EVE even with driver-mutations in the PI3K-Akt-mTor pathway.
Citation Format: Marcos Andre Costa, Marcelo Santos, Roberto Abramoff, Renata D'alpino, Carlos Teixeira, Ariel Kann, Jacques Tabacof, Riad Younes. Clinical outcomes of pts with advanced solid tumors treated according to NGS guided-therapy in a Brazilian cancer center [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2601.