Abstract 1276P
Background
Patients (Pts) with advanced NSCLC are eligible for treatments with immune checkpoint inhibitors (ICIs) as single agent or in combination with chemotherapy (ICI-CT), unless their tumor harbors actionable oncogenic drivers, more commonly observed in never-smokers. Next generation sequencing (NGS) is being increasingly employed in clinical practice in place of traditional molecular techniques, such as Real Time PCR (RT-PCR), mass spectrometry (MS) and fluorescence in situ hybridization (FISH), as ensures optimal levels of sensitivity and specificity.
Methods
We retrospectively assessed by NGS never-smoker NSCLC pts, who received ICIs between 2015 and 2020, most resulted negative from RT-PCR/MS for EGFR, KRAS, BRAF, ERBB2, PIK3CA mutational assessment and immunohistochemistry or FISH for ALK and ROS1 rearrangements. Tissue genotyping was performed through Oncomine Focus Assay®, a 52 genes targeted NGS panel that simultaneously analyzes DNA and RNA alterations. When tissue was unsuitable peripheral blood was tested by FoundationOne Liquid CDX®.
Results
Within our cohort of 276 NSCLC Pts treated with ICIs, 16 were never-smokers. Median age was 71.5 years (range 44-80), 11 were female, and most tumors were non-squamous (14/16). 6 Pts received ICI-CT in first-line, 2 pts received single-agent ICI in first-line and 8 received single-agent ICI in subsequent lines. Pts were tested with MS, 7 with RT-PCR; MS identified coexistent mutations of NRAS and KRAS in a Pt, and ERBB2 duplication in another. No further alterations were detected. NGS identified alterations in each evaluable Pt (13/16). In particular: DNA alterations in ERBB2 (2 gene amplifications, 4 insertions/duplications, 1 missense mutation), PIK3CA (2 missense mutations, 1 deletion), KRAS (n=2), CDK4 (n=1) and MYC (n=1) genes. RNA analysis showed RET fusions (n=2) and MET exon 14 skipping mutations (N=2). A Pt with RNA failed but available peripheral blood, resulted positive for ROS1 rearrangement.
Conclusions
NGS approach should be implemented upfront in current NSCLC management, especially in specific Pts subgroups more likely to harbor actionable oncogenic drivers, such as never-smokers, with potential impact on therapeutic approaches.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
IRCCS Ospedale Policlinico San Martino.
Funding
Has not received any funding.
Disclosure
C. Dellepiane: Other, Personal, Invited Speaker: AstraZeneca; Other, Personal, Invited Speaker: Bristol Myers Squibb; Other, Personal, Invited Speaker: Roche. M. Tagliamento: Other, Personal, Writing Engagements: Novartis; Other, Personal, Writing Engagements: Amgen; Other, Personal, Sponsor/Funding: Roche; Other, Personal, Sponsor/Funding: AstraZeneca; Other, Personal, Sponsor/Funding: Bristol Myers Squibb. G. Rossi: Other, Personal, Invited Speaker: Roche; Other, Personal, Invited Speaker: Novartis; Other, Personal, Invited Speaker: Amgen; Other, Personal, Invited Speaker: Janssen. C. Genova: Other, Personal, Invited Speaker: AstraZeneca; Other, Personal, Invited Speaker: Roche; Other, Personal, Invited Speaker: Boehringer Ingelheim; Other, Personal, Invited Speaker: Bristol Myers Squibb; Other, Personal, Invited Speaker: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.