Abstract
e15082 Background: Immune checkpoint inhibitor (ICI) therapy has become a mainstay of lung cancer treatment. However, not all NSCLC patients (pts) benefit, a subset paradoxically experience accelerated tumor growth while on immunotherapy. Hyperprogression (HP) refers to accelerated tumor growth on ICI with worsening clinical status. Various molecular alterations may be associated with HP including MDM2/MDM4 amplifications, EGFR aberrations, and STK11/LKB1 mutations. Kato et al. ( http://ow.ly/2n8a30nQpZv ) showed HP in 6/6 pts with MDM2/MDM4 amplification and in 2/10 pts with EGFR alterations. Methods: Lung cancer pts treated with ICI from Jan 2017 to Jan 2019 at Aurora Health Care were reviewed after IRB approved. Pts with NSCLC histology (ICD diagnosis codes and / or manual chart review), ICI treatment, and molecular testing were identified via the real world data (RWD) integrated in the Syapse platform. Additional chart review to ascertain HP was performed, and molecular results obtained via Syapse molecular lab integrations were analyzed. Pts had various forms of real world biomarker testing including oligo NGS panels. HP is defined as: 1) time-to-treatment failure (TTF) < 2 months (time from the start of treatment with ICI to ICI discontinuation for any reason, including progression, patient preference, toxicity, or death), 2) > 50% increase in tumor burden by RECIST, 3) spread of the disease to a new organ between baseline and first radiologic evaluation or clinical deterioration, and 4) ECOG PS ≥2 during the first 2 months of treatment. HP > = 3, Progression 1-2, non-progressor 0 criteria fulfilled.Pts with and without HP were compared using Chi-squared and Fisher Exact tests. T-tests were performed for continuous variables. Results: Out of 1536 lung cancer patients 350 (22.8%) were treated with ICI including: atezolizumab (35), durvalumab (6), nivolumab (177), pembrolizumab (145). Some pts were treated with more than one ICI. 64/350 (18.2%) pts had HP. 79/350 (22.5%) pts had progressive disease without meeting the definition of HP. Biomarker associations with HP are shown in the table. Conclusions: Only the STK11/LKB1 mutation was associated with HP (P = < 0.0001) with 5 of 6 STK11 pts treated with ICI showing HP. Other potential HP biomarkers will be assessed prospectively as larger panels are utilized. [Table: see text]
Published Version
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