Abstract P6-18-02: Primary and secondary results of the first nationwide molecular screening program in Spain for patients with advanced breast cancer (AGATA SOLTI-1301 study)
Authors: Pernas S , Villagrasa P , Nuciforo PG , Vivancos A , Scaltriti M , Rodón J , Burgués O , Canes J , Dueñas M , Cecchi F , Vidal M , Lluch A , Perelló A , Llombart A , Dorca J , Montaño A , Oliveira M , Ribas G , Rapado I , Paré L , Prat A , Ciruelos E 
Published: May 2019

Abstract
Background: Metastatic breast cancer is the second leading cause of death among women globally. A better understanding of tumor biology, and the availability of high-throughput technologies, have enabled the emergence of precision medicine bringing new expectations and giving rise to molecular screening programs (MSP). SOLTI, as a collaborative Spanish network, designed AGATA, the first multi-institutional MSP ever implemented in this country. Here, we report both the primary and some of the secondary results of the pilot study.
Methods: A total of 10 sites within SOLTI network in Spain participated. DNA-sequencing of 56 cancer related genes was performed using FFPE tumor samples (primary or metastatic). Each clinical case was reviewed by a multidisciplinary advisory board (MAB), which recommended, in a prospective manner, potential experimental treatments, mainly in the context of clinical trials. The primary objective was to determine the success rate of matching a DNA alteration to an experimental drug or drug class. Secondary objectives included a comprehensive molecular characterization of tumor samples by PAM50 subtyping and quantification of protein expression levels by MASS-SPEC (70 proteins panel).
Results: 305 patients (pts) were screened from September 2014 to July 2017 and 260 (85.3%) were finally evaluated by the MAB. Pts characteristics were: mean age 54 years (29-80), ER+/HER2- (n=192; 74%), HER2+ (n=30; 11.5%) and TNBC (n=38; 14.5%). 163 primary tumors and 97 metastatic samples were profiled. Regarding the primary objective, 116 pts (45%) presented at least one mutation (range 1-6) that could be matched to a drug or drug class. Of these, 13 pts (11.2%) received therapy matched to their molecular profile according to the MAB recommendation and their follow-up is still on-going. No mutation was detected in 97 (37%) pts (WT), and 47 patients (18.1%) presented a mutation but no match was possible. The most common mutations were PIK3CA (34%), TP53 (22%), AKT1 (5%), ESR1 (3%) and ERBB2 (3%). Intrinsic subtype distribution in 177 samples was as follows: 34% Luminal A (n=60); 21% Luminal B (n=36); 13% HER2E (n=22); 19% Basal-like (n=34) and 13% Normal-like (n=23). Compared to primary tumors (n=110), the proportion of HER2-enriched disease in metastatic tumors (n=63) was significantly higher (6% vs 20%; p=0.005). Protein expression analysis was performed in 146 samples (94 primary and 57 metastasis). In 19 cases (13%), the outlier expression of some targetable proteins (FGFR1 [n=4, 2.7%], IGF1R [n=4, 2.7%], EGFR [n=1, 0.7%], CEACAM5 [n=6, 4.1%], IDO1 [n=2, 1.37%], TROP2 [n=2, 1.37%]) were identified. Of note, HER2 overexpression (&gt;740 amol/μg) was observed in 4 HER2- cases. Finally, among WT tumors, 21% presented a potential drug-matched protein target.
Conclusions: Nationwide molecular screening in Spain is feasible. Nearly half of patients had tumors with mutation(s), mostly PIK3CA, that could be matched to a potential drug or drug class. PAM50 profile might be helpful to navigate towards a therapeutic decision making, although the MAB could not make any targeted-driven recommendation yet with this data. More clinical evidence is needed to use MASS-SPEC as a diagnostic tool.
Citation Format: Pernas S, Villagrasa P, Nuciforo PG, Vivancos A, Scaltriti M, Rodón J, Burgués O, Canes J, Dueñas M, Cecchi F, Vidal M, Lluch A, Perelló A, Llombart A, Dorca J, Montaño A, Oliveira M, Ribas G, Rapado I, Paré L, Prat A, Ciruelos E. Primary and secondary results of the first nationwide molecular screening program in Spain for patients with advanced breast cancer (AGATA SOLTI-1301 study) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-02.