Understanding clinical practice and survival outcomes in patients with unresectable stage III non-small-cell lung cancer in a single centre in Quebec.

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.

Retrospective cohort study of unresectable stage III non-small-cell lung cancer in Canada.

Background: The management of unresectable stage iii non-small-cell lung cancer (nsclc) is complex and best determined through multidisciplinary consultation. A longitudinal, population-level study was carried out to describe the management approach and outcomes of treatment in the real-world setting in Ontario. Methods: Individuals diagnosed with nsclc between 1 April 2010 and 31 March 2015 were identified in the Ontario Cancer Registry. Unresectable disease was defined as no surgery reported within 3 months of diagnosis. Initial treatments included radiotherapy (rt, curative or palliative), chemotherapy, targeted therapy, and chemoradiation [crt, concurrent (ccrt) or sequential (scrt)]. Survival was calculated from diagnosis with stage iii disease to death or last follow-up. Results: Of the 24,729 individuals diagnosed with nsclc, 5243 (21.2%) had stage iii disease, with most of the latter group (4542, 86.6%) having unresectable disease. Median age was 70 years, and 54.2% were men. The frequency of first-line treatment was ccrt, 22.1%; palliative rt, 21.0%; curative rt, 19.6%; no treatment, 19.6%; chemotherapy alone, 11.6%; scrt, 5.4%; and targeted therapy, 0.7%. Median overall survival (mos) was 14.2 months [95% confidence interval (ci): 13.6 months to 14.7 months], with the longest survival observed in patients who received targeted therapy (mos: 34.7 months; 95% ci: 21.4 months to 51.2 months), and the poorest, in those receiving no cancer treatment (mos: 5.9 months; 95% ci: 5.0 months to 6.4 months). The mos in patients receiving ccrt was 23.6 months (95% ci: 21.4 months to 25.6 months). Conclusions: Guideline-recommended ccrt is undertaken in only a small proportion of patients with unresectable nsclc in Ontario. The reasons for low uptake of that recommendation are only partly understood.

Real-world treatment patterns and survival in stage IV non-small-cell lung cancer in Canada.

Background: Almost half of all patients with non-small-cell lung cancer (nsclc) present with stage iv disease. The objective of the present study was to characterize treatment patterns and survival outcomes in patients with advanced nsclc. Methods: We conducted a longitudinal population-level study in patients diagnosed with stage iv nsclc in Ontario between 1 April 2010 and 31 March 2015, with follow-up to 31 March 2017 for overall survival and treatment sequence. Patients were stratified as nonsquamous or squamous histology. A sub-analysis was conducted for patients with nonsquamous histology who received targeted therapies, on the assumption that their tumours were EGFR mutation-positive (EGFRm+). Treatment patterns were determined, and survival was calculated from date of diagnosis to death or censoring. Results: Of 24,729 nsclc cases identified, stage iv disease was diagnosed in 49.2%, histology was nonsquamous in 10,103, and EGFRm+ was assumed in 508. Median patient age ranged from 69 to 72 years for the three cohorts. For patients with nonsquamous histology, palliative radiotherapy was the most frequently used first-line treatment (44.4%), followed by no treatment (26.7%) and chemotherapy (14.9%). In the EGFRm+ cohort, 75.6% received gefitinib as first- or second-line therapy, and almost half (47.4%) the 473 patients with squamous histology treated with first-line chemotherapy received cisplatin or carboplatin with gemcitabine. Median overall survival in the nonsquamous and squamous cohorts was 4.9 and 4.6 months respectively; it was 17.6 months for patients who were EGFRm+. Conclusions: Survival of patients with stage iv nsclc remains poor, with the exception of patients who are EGFRm+. Only 14.9% of patients received first-line chemotherapy; the mainstay of treatment was palliative radiotherapy.

Biopsy on progression in patients with EGFR mutation-positive advanced non-small-cell lung cancer-a Canadian experience.

Background: Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are standard therapy for patients with advanced or metastatic non-small-cell lung cancer harbouring an EGFR mutation. Upon progression, 50%-60% develop a secondary T790M mutation. Recent trials demonstrated outcome improvement with osimertinib compared with standard platinum-based chemotherapy as second-line therapy for patients with secondary T790M mutation. To identify T790M, a biopsy of the tumour or, more recently, plasma is necessary. This retrospective study aimed to evaluate biopsy procedures and mutational analysis at 2 Canadian cancer centres. Methods: In a retrospective review of patients who were approached to enrol in the aura2, aura3, or astris studies, demographics, eligibility for rebiopsy upon progression after an egfr tki, rebiopsy methods and complications, number of rebiopsies, and incidence of the T790M mutation were collected. Results: Of 84 patients considered for trial enrolment, 80 signed a consent. In 78 patients who underwent rebiopsy, computed tomography or ultrasonography guidance were the most common methods used. The most common biopsy sites were lung and lymph nodes. The median number of rebiopsies performed to find a T790M mutation was 2. Only 9% of patients experienced complications. Of samples obtained, 74% were adequate for testing after initial rebiopsy. A T790M mutation was found in 47 patients, of whom 44 were enrolled on a trial. After multiple rebiopsies, only 5% of samples were inadequate for molecular analysis. Conclusions: In the Canadian setting, the acceptance of rebiopsy on progression was high. Multiple rebiopsies were clinically feasible and could increase the yield for T790M mutation. The incidence of complications was low despite the most common site for rebiopsy being lung.

Cost-of-illness study for non-small-cell lung cancer using real-world data.

Background: With recent advances in the treatment of non-small-cell lung cancer (nsclc) and current fiscal constraints within publicly funded health care systems, understanding the real-world economic effect of lung cancer management has become important. The objective of the present study was to determine the costs and resources used in the management of nsclc cohorts in Ontario. Methods: Patients diagnosed between 1 April 2010 and 31 March 2015 were identified in the Ontario Cancer Registry and linked to provincial administrative databases, capturing resources such as hospitalizations, cancer clinic visits, physician services, and systemic therapies or radiotherapy. A cost-of-illness analysis using a bottom-up approach and the GETCOST macro available at ices determined the overall total and mean costs in 2017 Canadian dollars. Resource utilization results were analyzed according to the total number of encounters per resource, the number of patients using each resource, and the number of encounters per patient. A separate cost-and-resource analysis was conducted for radiotherapy. Results: The 24,729 nsclc patients identified included 4542 with stage iii unresectable disease and 10,103 with stage iv nonsquamous disease. The overall total cost for all nsclc patients was $1.9 billion, with inpatient hospitalizations ($635.2 million), cancer clinic visits ($323.7 million), and physician services ($301.4 million) being the top cost contributors. The mean cost per patient was $76,816. The total cost of radiotherapy was $38.5 million. Conclusions: Real-world costs for the management of nsclc during the 5-year period examined were substantial, despite the fact that median survival was poor and treatment information was limited.