Real-World Management and Outcomes of Crizotinib-Treated ROS1-Rearranged NSCLC: A Retrospective Canadian Cohort.

The use, safety and effectiveness of crizotinib as part of the management of ROS1-rearranged NSCLC patients in a real-world Canadian clinical cohort was the focus of this retrospective review. Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014-2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population where outcomes were similar to those described in other crizotinib-treated real-world cohorts, but lower than those of the PROFILE 1001 clinical trial population. Systemic anti-cancer therapy prior to crizotinib initiation occurred in half of the study cohort, with platin-pemetrexed and immune checkpoint inhibitors being most common. Platin-pemetrexed showed good effectiveness in this cohort, but despite high prevalence of upregulated PD-L1 expression, immune checkpoint inhibitors showed poor effectiveness in his cohort. Among all systemic therapies received, crizotinib showed the most effective disease control, although longer intervals between diagnosis and crizotinib initiation were more common among those showing a lack of clinical response to crizotinib, and patients with brain metastases at the time of crizotinib initiation also showed increased diagnosis to crizotinib initiation intervals and decreased clinical response to crizotinib. This study reveals crizotinib has clinical benefit, but timely identification of ROS1-rearrangements and initiation targeted therapies appears important to maximize outcome in this population.

Impact of Asian ethnicity on outcome in metastatic EGFR-mutant non-small cell lung cancer.

AIM: To determine factors associated with survival in de novo stage IV, non-small cell lung cancer (NSCLC) patients possessing epidermal growth factor receptor mutations (EGFRmut+ ) receiving tyrosine kinase inhibitors (TKI) in the first-line setting. METHODS: The Glans-Look Lung Cancer Database was used to retrospectively review stage IV EGFRmut+ NSCLC patients diagnosed 2010-2016 receiving first-line TKI. Patients with overall survival times in the upper quartile (≥34 months) were designated "long-term survivors" (LTS), the remaining deemed "average-term survivors" and characteristics between these groups were compared in univariate analysis, and multivariable models constructed to determine predictors of outcome. RESULTS: Of 170 eligible patients, median overall survival was 21 months. LTS were significantly more likely to be of Asian ethnicity, be never-smokers and not possess brain or bone metastases at diagnosis. Asian and non-Asian patients were comparable, save for an increased propensity of Asian patients to be never smokers and have normal-range BMI. Multivariable analysis revealed Asian ethnicity [hazard ratio (HR) = 0.65; P = 0.016] and never-smoking history (HR = 0.65; P = 0.034) as indicators of improved outcome, and presence of brain metastasis at diagnosis an indicator of poor outcome (HR = 2.21; P < 0.001). CONCLUSIONS: Analysis of this population-based cohort identifies never-smoking history and absence of brain metastasis along with Asian ethnicity as an independent prognosticators of favorable outcome, and reveals Asian patients to be clinicopathologically similar to non-Asian patients. These findings suggest Asian patients represent a unique subpopulation within EGFRmut+ NSCLC who may possess different biological underpinnings of NSCLC.

Comparison of Clinical Characteristics and Outcomes in Relapsed Versus De Novo Metastatic Non-Small Cell Lung Cancer.

OBJECTIVES: To compare the clinical characteristics and outcomes between relapsed and de novo metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We reviewed all NSCLC diagnoses between January 1999 and December 2013 in the institutional Glans-Look Lung Cancer Database, which contains demographic, clinical, pathologic, treatment, and outcome information. Patients with distant metastasis at diagnosis (American Joint Committee on Cancer [AJCC] eighth edition, stage IV), the "de novo" cohort, were compared with the "relapsed" cohort, consisting of patients diagnosed with early stage disease (stage I/II) undergoing curative intent treatment and subsequently experiencing metastatic relapse. Survival analysis, along with univariate and multivariable analysis was performed. RESULTS: A total of 185 relapsed and 3039 de novo patients were identified. Significantly different patterns of smoking history, histology, systemic therapy use, and disease extent were observed between the relapsed and de novo cohorts. Median overall survival from time of metastasis was significantly longer in relapsed than in de novo disease (8.9 vs. 3.7 mo, P<0.001). Relapsed patients demonstrated significant improvements in outcomes over time. In multivariate analysis, de novo metastatic disease continued to bode a worse prognosis (adjusted hazard ratio [HR], 1.4) as did male sex (HR, 1.2), never-smoking history (HR, 1.2), and presence of extrapulmonary metastases (HR, 1.3). Systemic therapy receipt conferred better outcome (HR, 0.4), although the impact of relapsed versus de novo disease on outcomes persisted regardless of systemic therapy receipt. CONCLUSIONS: Relapsed and de novo patients represent significantly different subpopulations within metastatic NSCLC with the latter exhibiting poorer survival. This information facilitates discussions about prognosis with patients and supports screening initiatives aimed at reducing de novo disease.

Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients.

PURPOSE: Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment. PATIENTS AND METHODS: We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut+) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurrence) stage IIIA-IV patients, as well as de-novo stage IV subset was analyzed. Multi-state modeling (MSM) and a Cox PH regression model with propensity score weights adjusted for clinicopathological variables between: diagnosis and PD and PD to death. RESULTS: 123 stage IIIA-IV patients were identified with 104 meeting RECIST-1.1-PD criteria. This RECIST-1.1-PD criteria subset included females (64.6%), Asians (39.4%), never/non-smokers (55.8%), and exon 19 deletion carriers (44.2%). Commonest treatment beyond initial-PD was continuing TKI alone (46/104), with another 21 patients continuing TKI plus additional systemic therapy. The median OS for patients who continued TKI treatment at initial-PD was 21.1 months versus 15.6 months for patients who discontinued TKI, p = 0.006. Via MSM analysis, continuing TKI at initial-PD followed by other systemic therapy was associated with an 83% reduced death risk, adjusted HR: 0.17 (95% CI: 0.07, 0.39). In the Cox PH model, ever-smokers with an exon 19 deletion had increased risk of death after PD (adjusted HR: 3.19, 95% CI: 1.54, 6.58), as did exon 21 mutation carriers, (adjusted HR: 2.10, 95% CI: 1.10, 4.00) and females (adjusted HR: 3.19, 95% CI: 1.54, 6.58). CONCLUSION: Subsequent systemic therapy after continuing TKI at initial-PD reduced the risk of death. Additionally, our data suggest that positive smoking history increases death risk for some EGFR mutation types and females.