Reality check for precision oncology in squamous cell lung cancer.

person Maham Bakhtyar UAMS-Winthrop Rockefeller Cancer Institute, Little Rock, AR info_outline Maham Bakhtyar, Sajjad Akbar Bhatti

Authors person Maham Bakhtyar UAMS-Winthrop Rockefeller Cancer Institute, Little Rock, AR info_outline Maham Bakhtyar, Sajjad Akbar Bhatti Organizations UAMS-Winthrop Rockefeller Cancer Institute, Little Rock, AR, UAMS Medical College Physicians Group, Little Rock, AR Abstract Disclosures Research Funding No funding received None. Background: Squamous cell lung cancer (SqCLC) is the second most common type of pulmonary malignancy after lung adenocarcinoma. Therapeutic advances in Precision Oncology have significantly improved outcomes in subsets of patients with lung adenocarcinoma. However, a significantly different mutational landscape has limited the success of Precision Oncology in SqCLC. Still, NCCN guidelines recommend considering molecular testing in SqCLC, preferably with broad-based molecular profiling like next-generation sequencing (NGS), aiming to identify candidates for FDA-approved targeted therapy. We aim to evaluate the percentage of SqCLC potentially eligible for targeted therapy using NGS by analyzing data from The Cancer Genome Atlas (TCGA). Methods: We filtered cases with a SqCLC diagnosis from the TCGA database. These cases were screened for DNA/RNA alterations in the 9 NCCN-guidelines recommended genes, including EGFR/ALK/ROS1/BRAF/MET/RET/HER2/NTRK/KRAS. Each unique alteration in the genes mentioned above was then analyzed in the oncoKB database to predict clinical benefit with level 1 and 2A evidence from FDA-approved targeted therapy. We then calculated the percentage of patients with SqCLC tested with NGS who could assess approved matched targeted therapy. Results: We identified 501 unique cases of SqCLC diagnosis in the TCGA. In the 9 NCCN-recommended actionable genes, 206 alterations were detected. We reviewed the clinical implication and utility of each of these alterations in the OncoKB database, and only 5 alterations were consistent with level 1/2A clinical benefit from a matched targeted therapy. These included 2 cases with L861Q and one each with EGFR L858R, EGFR E746_A750 exon 19 deletion, and G222C missense in the ERBB2 gene. Conclusions: The percentage of squamous cell cases which are potential candidates for FDA-approved targeted therapy was relatively low, 0.1% (5/501). While next-generation sequencing will not affect the standard of care treatment options for most SqCLC patients, clinicians can use this information to counsel patients for enrollment in clinical trials. Actionable gene mutations in squamous cell lung cancer. No. Genes Identified Total No. of Mutations No. of Actionable Mutations Actionable Mutations 1 EGFR 15 4 L861Q (2) L858R E746_A750del 2 ALK 20 3 ROS1 48 4 NTRK1 21 5 NTRK2 0 6 NTRK3 38 7 MET 9 8 RET 22 9 ERBB2 9 1 G222C 10 KRAS 9 11 BRAF 15 Total 206 5