No abstract

Background: To compare survival outcomes of patients with advanced or metastatic non-small cell lung cancer (NSCLC) who received immunotherapy as first-, second-or beyond line, versus matched patients receiving standard chemotherapy with special characterization of hyperprogressors. Methods: A retrospective cohort study of 296 patients with unresectable/metastatic NSCLC treated with either, first-, second-, third-or fourth-line of immunotherapy was conducted. A matched comparison with a historical cohort of first-line chemotherapy and a random forest tree analysis to characterize hyperprogressors was conducted. Results: Median age was 64 years (range 34-90), 40.2% of patients were female. A total of 91.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1. Immunotherapy as first-line was given to 39 patients (13.7%), second-line to 140 (48.8%), and as third-line and beyond to 108 (37.6%). Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival (PFS) of 4.27 months (95% CI 3.97-5.0). Factors associated with increased survival included treatment with immunotherapy as first-line (P < 0.001), type of response (P < 0.001) and PD-L1 status (P = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (P = 0.05) but not PFS (P = 0.2). A total of 44 hyperprogressors were documented (19.8%,.1%]). Leukocyte count over 5.300 cells/dL was present in both hyperprogressors and long-term responders. Conclusions: Patients who receive immune-checkpoint inhibitors as part of their treatment for NSCLC have better overall survival (OS) compared with matched patients treated with standard chemotherapy, regardless of the line of treatment.

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history. Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers ( n = 10) and never/ever-smokers ( n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models. Results: Median age was 63 years (46–81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases ( p = 0.04) and were older ( p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers ( p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5–34.6] vs. 17.3 months [4.8–29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41–0.80), limited-stage disease (HR 0.56, 95% CI 0.40–0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60–0.92) were independently associated with good prognosis. Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET , and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset.

Background: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-smallcell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations.Results: BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIMdel; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006).Methods: We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded

No abstract