Cell-Free Plasma DNA-Guided Treatment With Osimertinib in Patients With Advanced EGFR-Mutated NSCLC.

INTRODUCTION: Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non-small-cell lung cancer who have been pre-treated with EGFR-tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine. METHODS: From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non-small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients. RESULTS: T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92-3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89-5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers. CONCLUSION: Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.

First line crizotinib in anaplastic lymphoma kinase (ALK) rearranged squamous cell lung cancer.

Recently the superiority of Crizotinib to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC has been demonstrated. We report of a 36-year-old never smoker with advanced squamous cell carcinoma, presenting with a left lower lobe lesion, N3 nodal disease and multiple metastases (pleura, adrenal, muscle, bone). Despite squamous histology we decided on molecular testing. IHC for ALK was positive and confirmatory fluorescent in situ hybridization showed translocation of ALK. Although there is little evidence on ALK rearrangements in squamous NSCLC we decided on first line treatment with Crizotinib (250 mg twice daily). Eight and twelve weeks after treatment initiation a whole-body FDG fusion PET/CT scan showed dramatic tumor response with little remaining metabolic uptake in the left lobe and a single bone lesion. This evidence raises the question whether ALK testing should be done in never smokers with squamous NSCLC in the absence of oncogenic driver mutations. To our knowledge, this the first report of first line treatment of full squamous ALK-positive NSCLC with crizotinib.