In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9067-9067
Abstract:
9067 Background: Small cell lung cancer (SCLC) is an aggressive disease, characterized by inevitable chemotherapy resistance and rapid progression. We hypothesized that circulating tumor DNA (ctDNA) analysis can rapidly identify sensitivity to platinum-based therapy. Methods: Patients with SCLC at Memorial Sloan Kettering Cancer Center underwent serial plasma collections, including prior to the start of treatment and prior to Cycle 2 Day 1 of therapy (C2D1). Tumor mutations were identified from pre-treatment biopsies by MSK-IMPACT and/or pre-treatment plasma by CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). Median variant allele fraction (VAF) of all mutations was monitored on subsequent blood draws using CAPP-Seq. Progression free survival (PFS) was measured from the time of first pre-treatment blood draw. Results: Plasma was collected from 19 patients treated with carboplatin and etoposide, including three who received concurrent atezolizumab. Seven were female, and mean age was 64.5 years. ctDNA was detected in 17 patients (89%), including in the two patients in our series with limited stage disease. The most common mutations were in TP53 and RB1 in 14 and 6 patients, respectively. Fourteen patients had available plasma at C2D1. At baseline prior to treatment, median VAF did not differ significantly between radiologic responders and non-responders (9.4% versus 30.3%, p = 0.35). After one cycle of chemotherapy, the VAF percent decrease was significantly more in responders versus non-responders (-96.9% versus -10.3%, p 〈 0.001). Median VAF was therefore significantly lower by C2D1 in patients who responded compared to non-responders (0.51% versus 27.2%, p = 0.02). Those who ultimately responded to therapy all had a 〉 2 fold decrease in VAF by C2D1. With a median follow-up of 180 days, PFS was significantly longer in patients with 〉 2 fold decrease in VAF by C2D1 (6.4 versus 1.9 months, log rank p 〈 0.001). Conclusions: A 2-fold decrease in plasma VAF by C2D1 predicted platinum-sensitivity in SCLC and was associated with longer PFS. ctDNA may permit early assessment of benefit and expedite alternative treatment options for those without significant decrease in median VAF after one cycle of therapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.9067
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
