A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups.

BACKGROUND: We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer. PATIENTS AND METHODS: 125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype, and survival were assessed. RESULTS: 51/125 patients (40.8%) were total CTC+ and 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with ≥5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with <5 total CTCs. No OS difference was evident between vim+ CTC and vim-negative CTC patients overall (HR 1.24, 95% CI 0.67-2.28, P = 0.494), but after subdivision according to NSCLC driver mutation, we found an increase of vim+ CTCs in the EGFR-mutated subgroup (N = 21/94 patients; mean 1.24 vs 1.22 vim+ CTCs, P = 0.013), a reduction of total CTCs in the ALK-rearranged subgroup (N = 13/90 patients; mean 1.69 vs 5.82 total CTCs, P = 0.029), and a total absence of vim+ CTCs in KRAS-mutated adenocarcinomas (N = 19/78 patients; mean 0 vs 1.4 vim+ CTCs, P = 0.006). CONCLUSIONS: We validate that the baseline presence of ≥5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma.

Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.

Background: Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. Material and methods: ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA. Results: The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively. Conclusion(s): ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue.

Activity and safety of oral etoposide in pretreated patients with metastatic or recurrent thymic epithelial tumors (TET): A single-institution experience.

OBJECTIVES: Standard regimens in pretreated advanced TETs are lacking. Single agent responses have been reported with pemetrexed, gemcitabine and targeted therapies. Oral etoposide monotherapy has a favorable safety and efficacy profile in other tumor types. We assessed its activity and safety in advanced or recurrent pretreated TETs. PATIENTS AND METHODS: We conducted a retrospective analysis of patients with advance or recurrent TET treated with single agent oral etoposide at Gustave Roussy (GR) between 1992 and 2015. Efficacy analyses was made by treating physician according to RECIST and retrospectively collected from medical records. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty patients were included. Median age was 62 years [range 34-88], 60% were male, 25% had thymoma (T) and 75% had thymic carcinoma (TC). Myasthenia gravis was reported in 15% of them. A median of 2 [range 0-7] prior chemotherapy regimens had been administered, with 60% exposed to etoposide (VIP 40%, carboplatin-etoposide 15%, BEP 5%). Median follow-up since etoposide was 7 years [range 0.5-8.9]. Three patients achieved partial response and nine had stable disease, giving an overall response rate of 15% [T: 20%, TC: 13%] and a 60% disease control rate [T: 100%, TC: 46%]. Median PFS was 4 months [95%CI 3-14] and median OS was 41 months [95%CI 6-86]. Median PFS for T and TC were 21 months [95%CI 9-42] and 4 months [95%CI 2-4]; median OS were 99 months [95%CI 43-not reached] and 13 months [95%CI 4-41], respectively. The most common grade 3-4 related events occurred in 9 patients (45%) and were neutropenia followed by anemia and thrombocytopenia. CONCLUSION: Oral etoposide monotherapy is an active option for pretreated TET patients, with manageable toxicity profile.

Thymic malignancies: Moving forward with new systemic treatments.

Thymic neoplasms are rare malignant tumours, for which the mainstay of treatment is surgical resection. Platinum-based chemotherapy remains the principal treatment in metastatic tumours, with no standard second-line option. Many genes implicated in tumour onset, growth and metastases have been demonstrated to be therapeutic targets in thymic malignancies. Other current efforts to improve outcomes are based on a better understanding of the stromal compartment and tumour microenvironment, facilitating novel therapeutic approaches such as angiogenesis inhibition and immunotherapy. This review seeks to explore the present cutting edge for systemic treatment of advanced thymic neoplasms, examining novel agents under clinical investigation such as cytotoxic therapies, targeted therapies and immunotherapy. Based on the literature review we have selected potential treatment schemes, which could be used in daily clinical practice as second-line treatment.