Abstract
Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: The IMMINENT study.
Author
person
Marco Sposito
University of Verona, Oncology Section, Verona, Italy, Italy
info_outline
Marco Sposito, Lorenzo Belluomini, Jessica Insolda, Alessandra Dodi, Giuseppe Aprile, Antonello Veccia, Orazio Caffo, Hector Josè Soto Parra, Fiorella Lombardo, Antonio Lugini, Mario Occhipinti, Francesco Ferrau, Clementina Savastano, Francesco Verderame, Emilio Bria, Silvia Novello, Umberto Malapelle, Sara Pilotto, Michele Milella
Full text
Authors
person
Marco Sposito
University of Verona, Oncology Section, Verona, Italy, Italy
info_outline
Marco Sposito, Lorenzo Belluomini, Jessica Insolda, Alessandra Dodi, Giuseppe Aprile, Antonello Veccia, Orazio Caffo, Hector Josè Soto Parra, Fiorella Lombardo, Antonio Lugini, Mario Occhipinti, Francesco Ferrau, Clementina Savastano, Francesco Verderame, Emilio Bria, Silvia Novello, Umberto Malapelle, Sara Pilotto, Michele Milella
Organizations
University of Verona, Oncology Section, Verona, Italy, Italy, Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy, Verona, Italy, Italy, University of Verona, Oncology Section, Verona, Italia, Italy, Medical oncology, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy, Italy, Oncologia Medica - Ospedale San Bortolo Azienda ULSS8 Berica, Vicenza, Italy, Italy, Santa Chiara Hospital, Trento, Italy, Italy, APSS Santa Chiara Hospital, Trento, Italy, Italy, Policlinico Universitario Gaspare Rodolico, Catania, CT, Italy, Ospedale P.Pederzoli Peschiera del Garda, Verona, Italy, Italy, Ospedale San Giovanni Addolorata, Rome, Italy, Italy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Department of Oncology - San Vincenzo Hospital, Taormina, Italy, Italy, UO Oncologia OSP: Ruggi D'Aragona, Salerno, Italy, Italy, AO Ospedali Riuniti PO Vincenzo Cervello, Palermo, ITALY, Italy, Universita Cattolica Del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy, Italy, Ospedale S Luigi, Orbassano, CN, Italy, University of Naples "Federico II", Napoli, Italy, Italy, Section of Oncology, University of Verona, School of Medicine and Verona University Hospital Trust, Verona, Italy, Italy
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Roche
Background:
NGS-based profiling is the current standard for the molecular characterization of advanced NSCLC (aNSCLC) in clinical practice. Here we report the results of tissue- and liquid-biopsy based NGS, using FoundationOne and FoundationLiquid CDx (FM1/FM1L), in the context of a multicenter national access program in a cohort of aNSCLC patients (pts).
Methods:
Genomic evaluation was performed on FFPE-tumor blocks or blood samples, using FM1 (324 genes) for tissue samples or FM1L (70 genes) for liquid biopsy. Tumor mutational burden (TMB) and microsatellite instability were also evaluated. The aim of this analysis was to investigate the real-world frequency of molecular alterations in aNSCLC and their correlation with patients’ clinical and pathological characteristics.
Results:
Overall, 232 aNSCLC pts from 11 different institutions were gathered [median age 63 years, never/former or current smokers 29/66%, Performance Status 0-1 93%, adenocarcinoma/squamous 79/13%, metastasis at diagnosis 70%]. 138 pts (59.5%) underwent FM1 and 94 (40.5%) FM1L analyses. Alterations were found in 170 different genes. Median number of mutated genes per sample was 4 (IQ 3-6) in FM1 cohort and 2 (IQ 1-3) in FM1L cohort. In 13 FM1L samples (5.6%) no genetic alterations were detected. In unselected pts, TP53 (57.8%), KRAS (22%), CDKN2A/B (19%) and STK11 (17.2%) alterations were among the most frequently detected. Percentages of ALK, HER2, RET, MET, BRAF, NTRK and ROS1 alterations were 4.3, 4.3, 3.4, 3.0, 2.6, 1.3, 0.9, respectively. Among EGFR-mutant pts (15.1%), in both FM1 and FM1L cohorts, ex19del (31.3/35.7%), L858R (12.5/14.3%) and T790M (0/14.3%) were the most frequently detected. Among KRAS-mutant pts, G12C was the mutation most frequently detected (37%). Alterations in KEAP1 were significantly associated with STK11, SMARCA4 and KRAS alterations. Significant associations between TP53 and RB1 alterations were also detected. Median TMB was 6 (0-100) and was significantly higher in current/former smokers. Median OS was 19.6 months (IQ 6.9-36.1), and significantly lower in pts harboring ≥3 gene mutations.25 pts (10.8%) received target therapy on the basis of molecular profiling with FM1/FM1L. In this subgroup, EGFR was the most frequently actionable gene alteration detected (9), followed by RET (4), ALK (3), KRAS (2), MET (2), NTRK (2), BRAF (1), BRCA (1) and HER2 (1).
Conclusions:
This analysis confirms that NGS-based molecular profiling (on either tissue or blood samples) of aNSCLC provides important prognostic and predictive information, possibly increasing treatment opportunities. Further analyses will focus on actionable alterations in potentially clinically relevant genes outside
“the usual suspects”
. In the awareness of the urgent need for real world data and to implement NGS, ATLAS (https://biomarkersatlas.com/) will certainly be a fundamental tool.
14 organizations
1 product
19 drugs
19 targets
Organization
University of Verona, Oncology SectionOrganization
Santa Chiara Hospital, Trento, ItalyOrganization
Policlinico Universitario Gaspare RodolicoOrganization
Ospedale P.Pederzoli Peschiera del GardaOrganization
Ospedale San Giovanni AddolorataOrganization
San Vincenzo HospitalOrganization
AO Ospedali Riuniti PO Vincenzo CervelloOrganization
Universita Cattolica Del Sacro CuoreOrganization
Ospedale S LuigiDrug
FM1Drug
FM1LDrug
TP53Drug
KRASDrug
CDKN2A/BDrug
STK11Drug
MelphalanDrug
HER2 CAR-TDrug
RET TKIsProduct
TMZDrug
BRAFDrug
NTRKiDrug
ROS1 TKIsDrug
KEAP1Drug
SMARCA4Drug
RB1Drug
BRCATarget
CDKN2BTarget
ALKTarget
NTRRTarget
RB1Target
HER2 (ERBB2)Target
BRCA1Target
KRAS G12CTarget
BRAFTarget
STK11Target
SMARCA4Target
metastatic breast cancerTarget
STK11/LKB1Target
KEAP1Target
CDKN2A/BTarget
ROS1Target
RETTarget
NTRKTarget
TP53