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Plasma next-generation sequencing (NGS) in advanced non-small cell lung cancer (aNSCLC) patients (pts) treated with immune checkpoint inhibitors (ICIs): Impact of STK11 and TP53 mutations on outcome.

Abstract

3046
Background: ICIs revolutionized aNSCLC treatment. The next challenge lays on the search for predictive markers. Detection of multiple tumor-related genetic alterations through NGS in cell free DNA is a promising tool, provided the limited availability of tumor tissue in most cases. Methods: Between January 2017 and October 2019, aNSCLC pts consecutively referring to our Institution were prospectively screened with plasma NGS while included in two clinical trials: VISION (NCT02864992) and MAGIC trial, an observational study. In VISION trial NGS was performed in plasma (Guardant360 test) and tissue (Oncomine Focus Assay). In MAGIC Myriapod NGS-IL 56G Assay was used. Aim of the study was to evaluate the impact of STK11, KRAS and TP53 mutations (muts) on outcome of ICI-treated pts, with overall survival (OS) as primary endpoint. A control group of pts not receiving ICIs was also analyzed. Results: A total of 235 NSCLC pts were enrolled and received ICIs. 93 pts were analyzed in plasma at the time of beginning ICIs: median OS was 18.9 m (95% CI: 13.7-24.1) and median immune-related progression free disease (irPFS) 3.8 m (95% CI: 2.5-5.1). 49 (52.7%), 22 (23.7%) and 8 (8.6%) pts carried TP53, KRAS and STK11 pathogenic alterations, respectively. STK11 mutated pts showed a trend for worse OS compared with wildtype counterpart (14.9 m, 95% CI: 6.5-23.3, versus 20.3, 95% CI: 13.4-27.2, p = 0.192) KRAS muts had no impact on outcome. Pts with TP53 or STK11/KRAS co-mut (n = 3) had worse OS (12.3 m, 95% CI: 9.2-15.4; HR = 3, 95% CI: 1.6-5.8, p = 0.001 and 5.9 m, 95% CI: 1.4-7.6; HR = 2.9, 95% CI: 1.4-6.3, p = 0.007) and worse irPFS (2.8 m, 95% CI: 1.7-3.9, HR = 1.8 95% CI: 1.1-3.1, p = 0.03 and 1.2 m, 95% CI: 0.9-1.5, HR = 2.2 95% CI: 1.2-4.1, p = 0.01). Number of muts negatively impacts pts’ OS (HR = 1.2, 95% CI: 1.1-1.3, p = 0.02) and was higher among TP53 mutated pts (p < 0.001, Mann-Whitney test). In multivariate analysis, TP53 and STK11/KRAS retained significance. A control group of pts not receiving ICIs was analyzed (n = 101): median OS was 16.8 m (95% CI: 13-20.6). Nor STK11 (n = 10), nor STK11/KRAS (n = 6) had impact on OS (HR = 1.8, 95% CI: 0.7-4.7, p = 0.267 and 1.4, 95% CI: 0.7-3.0, p = 0.293) while the presence of TP53 muts (n = 41) was associated with shorter OS (11.4 m, 95% CI: 7.3-15.5; HR = 2.2, 95% CI: 1.2-4.2, p = 0.009). Conclusions: NGS performed in plasma might be used to detect predictive markers. TP53 muts in plasma at baseline had prognostic value, while STK11/KRAS muts were associated with worse outcome to ICIs.

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Journal of Clinical Oncology
Pages: 3046

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Published in print: May 20, 2020
Published online: May 25, 2020

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Alberto Pavan
Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy;
Elisabetta Zulato
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy;
Lorenzo Calvetti
Department of Oncology, San Bortolo General Hospital, ULSS8 Berica - East District, Vicenza, Italy, Vicenza, Italy;
Alessandra Ferro
Department of Surgery, Oncology and Gastroenterology, University of Padua and Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy;
Giorgia Nardo
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy;
Alice Boscolo
Department of Surgery, Oncology and Gastroenterology, University of Padua and Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy;
Ilaria Attili
Department of Surgery, Oncology and Gastroenterology, University of Padua and Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy;
Stefano Frega
Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy;
Alessandro Dal Maso
Department of Surgery, Oncology and Gastroenterology, University of Padua and Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy;
Giulia Pasello
Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy;
Valentina Guarneri
Department of Surgery, Oncology and Gastroenterology, University of Padua and Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy;
Giuseppe Aprile
Department of Oncology, San Bortolo General Hospital, ULSS8 Berica-East District, Vicenza, Italy;
Pier Franco Conte
Department of Surgery, Oncology and Gastroenterology, University of Padova and Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy;
Stefano Indraccolo
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy;
Laura Bonanno
Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy;
Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; Department of Oncology, San Bortolo General Hospital, ULSS8 Berica - East District, Vicenza, Italy, Vicenza, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua and Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy; Department of Oncology, San Bortolo General Hospital, ULSS8 Berica-East District, Vicenza, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova and Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy

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Alberto Pavan, Elisabetta Zulato, Lorenzo Calvetti, Alessandra Ferro, Giorgia Nardo, Alice Boscolo, Ilaria Attili, Stefano Frega, Alessandro Dal Maso, Giulia Pasello, Valentina Guarneri, Giuseppe Aprile, Pier Franco Conte, Stefano Indraccolo, Laura Bonanno
Journal of Clinical Oncology 2020 38:15_suppl, 3046-3046

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