Abstract 560: High levels of baseline ctDNA constitute a poor prognostic factor in progression-free survival in patients receiving neo-adjuvant chemo-immunotherapy: Results from NADIM clinical trial
Authors: Provencio Mariano , Serna-Blasco Roberto , Nadal Ernest , Insa Amelia , Garcia-Campelo M. Rosario , Corbacho Diego Pereiro , Domine Manuel , Majem Margarita , Rodriguez-Abreu Delvys , Martinez-Marti Alex , de Castro Javier , Cobo Manuel , Lopez-Vivanco Guillermo , del Barco Edel , Bernabe Reyes , Viñolas Nuria , Barneto Isidoro , Viteri Santiago , Pereira Eva , Royuela Ana , Casarrubios Marta , Salas Clara , Parra Edwin R , Wistuba Ignacio , Calvo Virginia , Laza-Briviesca Raquel , Massuti Bartomeu , Cruz-Vermudez Alberto , Romero Atocha 
Published: July 2021

Abstract
There is growing evidence supporting that long-term survival of neoadjuvant chemo-immunotherapy for locally advanced NSCLC patients can be achieved. However, some patients invariably progress within the short-term. Identification of patients at high risk of progression is needed to achieve a better control of the disease. Concentrations of baseline ctDNA have been shown to be of prognostic significance.
Patients and methods 42 pre-treatment plasma samples from the NADIM clinical trial (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with Nivolumab, were analyzed by NGS, using the Oncomine Pan-Cancer Cell-Free Assay™ (Thermo Fisher Scientific®). Variant calling, annotation and filtering were performed on the Ion Reporter (v5.14) platform using the OncomineTagSeq Pan-Cancer Liquid Biopsy workflow (v2.3). The final variant matrix was obtained from vcf files as generated from Ion Reporter (v5.14) platform and applying an internal pipeline (R-code is available upon request). Progression disease was evaluated by RECIST criteria V1.1.
Results A total of 116 variants were detected in 88.10% (N=37) of the plasma samples collected before neoadjuvant treatment. The average number of variants detected per sample was 3.13. The most frequently mutated genes were TP53, which accounts for 59.52% of the detected variants, followed by PIK3CA (30.95%), MAP2K1 (30.95%), APC (23.81%), MTOR (9.52%) and KIT (9.52%). Patients in whom a GNA11 mutation was detected in the plasma sample by NGS showed worsen progression free survival (PFS) (HR: 14. 95%; CI: 2.6-71, P-value with Fold Discovery Rate correction: 0.019). Finally, ctDNA levels at Mutant Allele Frequency (MAF) below 1% at baseline were associated with improved PFS (P=0.025). At 30 months, PFS was 80.30% for these patients compared with 58.33% in patients with ctDNA levels ≥ 1%.
Conclusions Molecular profiling of liquid biopsies collected before neoadjuvant chemo-immunotherapy using NGS can identify patients at high risk of progression who might require more aggressive adjuvant treatment in order to achieve a better control of the disease.
Citation Format: Mariano Provencio, Roberto Serna-Blasco, Ernest Nadal, Amelia Insa, M. Rosario Garcia-Campelo, Diego Pereiro Corbacho, Manuel Domine, Margarita Majem, Delvys Rodriguez-Abreu, Alex Martinez-Marti, Javier de Castro, Manuel Cobo, Guillermo Lopez-Vivanco, Edel del Barco, Reyes Bernabe, Nuria Viñolas, Isidoro Barneto, Santiago Viteri, Eva Pereira, Ana Royuela, Marta Casarrubios, Clara Salas, Edwin R Parra, Ignacio Wistuba, Virginia Calvo, Raquel Laza-Briviesca, Bartomeu Massuti, Alberto Cruz-Vermudez, Atocha Romero. High levels of baseline ctDNA constitute a poor prognostic factor in progression-free survival in patients receiving neo-adjuvant chemo-immunotherapy: Results from NADIM clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 560.