Jeff Lewis

P3.01-109 Real-World Patient-Reported Outcome Assessment of Patients with Metastatic Non-Small Cell Lung Cancer

1 72/Male Blood No No No treatment Not applicable Not applicable 2 62/Male Tissue No KRAS p.G12A, STK11 p.D53Gfs*110 Chemotherapy Not available Not available 3 62/Male Tissue No EGFR p.L747_T751del (EX19del) Gefitinib PR 20+ 4 63/Female Tissue No EGFR p.L858R (EX21) Gefitinib PR 5+ 5 75/Female Tissue No EGFR p.L858R (EX21) Icotinib SD 11+ 6 63/Male Blood Icotinib EGFR p.L858R (EX21),CHEK2 c.4451G>A Combined gefitinib and bevacizumab SD 6+

Local Consolidation Therapy (LCT) After First Line Tyrosine Kinase Inhibitor (TKI) for Patients With EGFR Mutant Metastatic Non–small-cell Lung Cancer (NSCLC)

Introduction: Although most NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutations have an impressive initial response, the vast majority has residual disease and develops acquired resistance after 9 to 14 months of EGFR tyrosine kinase (TKI) therapy. We recently reported a phase II trial showing that, for patients with molecularly unselected oligometastatic NSCLC who did not progress after first‐line systemic therapy, local consolidation therapy (LCT) with surgery or radiation improved progression‐free survival (PFS), compared with maintenance therapy alone. Herein, we report a retrospective analysis of LCT after TKI in patients with metastatic EGFR mutant NSCLC. Patients and Methods: We identified patients with metastatic EGFR mutant NSCLC treated with TKI plus LCT or with TKI alone in the MD Anderson GEMINI (Genomic Marker‐Guided Therapy Initiative) database and in our recently published LCT trial. PFS was compared between LCT plus TKI and TKI only treated patients using the log‐rank test. Results: We identified 129 patients with EGFR mutant NSCLC who were treated with first‐line TKI and 12 that were treated with TKI followed by LCT. Among the 12 patients treated with TKI plus LCT, 8 patients had oligometastatic disease (defined as ≤ 3 metastases), and 4 patients had > 3 metastases. LCT regimens were hypofractionated radiotherapy or stereotactic ablative body radiotherapy for 11 patients and surgery for 1 patient. TKI followed by LCT resulted in a significantly longer PFS (36 months) compared with TKI alone (PFS, 14 months; log‐rank P = .0024). Conclusions: Our data suggests that first‐line TKI plus LCT is a promising therapeutic strategy for patients with EGFR mutant NSCLC that merits further investigation.

Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations

Background: Major guidelines do not recommend routine molecular profiling of lung squamous‐cell carcinoma (LUSC) because the prevalence of actionable alterations is thought to be low. Increased utilization of next‐generation sequencing (NGS), particularly with cell‐free circulating tumor DNA, facilitates reevaluation of this premise. Patients and Methods: We retrospectively evaluated the prevalence of actionable alterations in 2 distinct LUSC cohorts totaling 492 patients. A total of 410 consecutive patients with stage 3B or 4 LUSC were tested with a targeted cell‐free circulating DNA NGS assay, and 82 patients with LUSC of any stage were tested with a tissue NGS cancer panel. Results: In the overall cohort, 467 patients (94.9%) had a diagnosis of LUSC, and 25 patients (5.1%) had mixed histology with a squamous component. A total of 10.5% of the LUSC subgroup had somatic alterations with therapeutic relevance, including in EGFR (2.8%), ALK/ROS1 (1.3%), BRAF (1.5%), and MET amplification or exon 14 skipping (5.1%). Sixteen percent of patients with mixed histology had an actionable alteration. In the LUSC subgroup, 3 evaluable patients were treated with targeted therapy for an actionable alteration; all of them experienced partial response. Conclusion: In this large, real‐world LUSC cohort, we observed a clinically significant prevalence of actionable alterations. Accurate local histopathologic assessment in advanced‐stage LUSC can be challenging. Further evaluation of the genomic landscape in this setting is warranted to potentially identify underappreciated treatment options.