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The discovery of EGFR tyrosine kinase inhibitors (TKI) for the treatment of EGFR mutant (EGFRm) metastatic NSCLC is regarded as a landmark in lung cancer. EGFR-TKIs have now become a standard first-line treatment for EGFRm NSCLC. The aim of this retrospective cohort study is to describe real-world patterns of treatment and treatment outcomes in patients with EGFRm metastatic NSCLC who received EGFR-TKI therapy outside of clinical trials. One hundred and seventy EGFRm metastatic NSCLC patients were diagnosed and initiated on first-line TKI therapy between 2004 and 2018 at the Peter Brojde Lung Cancer Centre in Montreal. Following progression of the disease, 137 (80%) patients discontinued first-line treatment. Moreover, 80/137 (58%) patients received second-line treatment, which included: EGFR-TKIs, platinum-based, or single-agent chemotherapy. At the time of progression on first-line treatment, 73 patients were tested for the T790M mutation. Moreover, 30/73 (41%) patients were found to be positive for the T790M mutation; 62/80 patients progressed to second-line treatment and 20/62 were started on third-line treatment. The median duration of treatment was 11.5 (95% CI; 9.62-13.44) months for first-line treatment, and 4.4 (95% CI: 1.47-7.39) months for second-line treatment. Median OS from the time of diagnosis of metastatic disease was 23.5 months (95% CI: 16.9-30.1) and median OS from the initiation of EGFR-TKI was 20.6 months (95% CI: 13.5-27.6). We identified that ECOG PS ≤ 2, presence of exon 19 deletion mutation, and absence of brain metastases were associated with better OS. A significant OS benefit was observed in patients treated with osimertinib in second-line treatment compared to those who never received osimertinib. Overall, our retrospective observational study suggests that treatment outcomes in EGFRm NSCLC in real-world practice, such as OS and PFS, reflect the result of RCTs. However, given the few observational studies on real-world treatment patterns of EGFR-mutant NSCLC, this study is important for understanding the potential impact of EGFR-TKIs on survival outside of clinical trials. Further real-world studies are needed to characterize patient outcomes for emerging therapies, including first-line osimertinib use and combination of osimertinib with chemotherapy and potential future combination of osimertinib and novel anticancer drug, outside of a clinical trial setting.

Methods: A retrospective cohort study considered patients 18 or more years of age diagnosed between January 2007 and May 2018 with unresectable stage iii non-small-cell lung cancer (nsclc) who received combined chemoradiation (crt). Survival was analyzed using the Kaplan-Meier method to determine median overall (os) and progression-free survival (pfs) and the associated 95% confidence intervals (cis). Cox regression analysis was performed to identify factors prognostic for survival, including age, sex, smoking status, Eastern Cooperative Oncology Group performance status (ecog ps), histology, treatment type, tumour size, and nodal status., Results: Of 226 patients diagnosed with unresectable stage iii disease, 134 (59%) received combined crt. Mean age was 63 years; most patients were white, were current smokers, had an ecog ps of 0 or 1, and had nonsquamous histology. Median pfs was 7.03 months (95% ci: 5.6 months to 8.5 months), and os for the cohort was 18.7 months (95% ci: 12.4 months to 24.8 months). Of those patients, 78% would have been eligible for durvalumab consolidation therapy. Univariate analysis demonstrated a significant os benefit ( p = 0.010) for concurrent crt (ccrt) compared with sequential crt (scrt). Disease-specific survival remained significantly better in the ccrt group ( p = 0.004). No difference in pfs was found between the ccrt and scrt groups. In addition, tumour size and nodal involvement were significant discriminating factors for survival ( p < 0.05). In this patient cohort, 64% of patients progressed and received subsequent therapy. Based on multivariate analysis, tumour size and nodal station were the only factors predictive of survival in patients with unresectable stage iii nsclc treated with crt., Conclusions: Combined crt has been the standard treatment for unresectable stage iii nsclc. In our study, a trend of better survival was seen for ccrt compared with scrt. Factors predictive of survival in patients with stage iii disease treated with crt were tumour size and nodal station. Most patients with stage iii disease would potentially be eligible for durvalumab maintenance therapy based on the eligibility criteria from the pacific trial. The use and effectiveness of novel treatments will have to be further studied in our real-world patient population and similar populations elsewhere., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests: MH and RNW are employees of AstraZeneca Canada. The remaining authors have no conflicts to disclose., (2020 Multimed Inc.)

Background: Platinum-based chemotherapy is standard treatment for patients with advanced lung cancer. The common side effect of this therapy is myelosuppression, for which different stimulating factors are used. In this article, the effect of granulocyte colony-stimulating factor (G-CSF) administration on the survival of patients with unresectable non-small-cell lung cancer (NSCLC) was evaluated., Methods: The charts of 127 patients, treated with carboplatin-based chemotherapy, were reviewed for histology, stage, performance status, weight loss, treatment regimen, toxicity, and survival. Eighty patients were stage IIIA/IIIB NSCLC; 47 were stage IIIB (pleural effusion) or stage IV. Eighty-one patients (63%) experienced severe (grades 3 and 4) neutropenia. Forty-two patients received G-CSF, 37 patients for severe neutropenia (14 with febrile neutropenia) and five patients for active infection during chemotherapy., Results: Preliminary analyses, both unadjusted (median survival, 20 months versus 13.8 months; log-rank test, p = 0.02) and adjusted for covariates of interest (Cox regression, hazard ratio = 0.62, p = 0.03) showed a significant effect of the use of G-CSF on survival, even though the groups were balanced with respect to stage, performance status, weight loss, and dose intensity of chemotherapy. Patients with grades 3 and 4 neutropenia (whether they received G-CSF or not) had a better survival outcome compared to those who did not have neutropenia (median survival, 17.6 months versus 11.9 months, log-rank test, p = 0.04). A landmark analysis showed a marginally significant effect of G-CSF on survival (median survival, 18.6 months versus 15.1 months, log-rank test, p = 0.08), even after adjustment for covariates. The Cox regression with the use of G-CSF defined as a binary time-varying covariate also showed similar results (Cox regression, hazard ratio = 0.67, 95% CI: 0.42-1.04, p = 0.07)., Conclusion: In this study, the time bias due to the delayed administration of G-CSF contributed to the longer survival of patients receiving G-CSF. Prospective studies are required to determine whether G-CSF has any effect on survival in patients with advanced NSCLC.

In Europe, the squamous cell carcinoma is the most frequent non-small cell lung cancer (NSCLC) subtype and until now, no increase in incidence of lung adenocarcinoma (ADC) has been described (except in the Netherlands), in contrast to North America where ADC predominates. Our aim was to compare the percentage of ADC in Montreal (MTL), Canada, with that in Strasbourg (STBG), France. We prospectively identified patients with NSCLC in MTL and in STBG over an 8-month period and described the distribution of NSCLC by sex, age, subtype and smoking history. A total of 172 patients in MTL and 166 in STBG were identified. The male/female ratio was significantly different in STBG (12:1) and in MTL (2:1). The percentage of ADC was significantly higher in MTL (40%) than in STBG (30%). This difference is partly due to the higher number of women with NSCLC in Montreal combined with the predominance of ADC in women. The proportion of ADC decreased with age in STBG, but was similar in each age category in MTL. In STBG, most women with NSCLC had never smoked (69%), in contrast to MTL where only 16% of women had never smoked. In conclusion, ADC is more frequent in MTL than in STBG. This is partly due to the higher number of women with NSCLC in MTL combined with the predominance of ADC in women. The greatest proportion of ADC subtype in the youngest cohorts of men in STBG suggests that ADC may be on the rise in this city.