Background/Aim: Lung cancer remains the main culprit in cancer-related mortality worldwide. Transcript fusions play a critical role in the initiation and progression of multiple cancers. Treatment approaches based on specific targeting of discovered driver events, such as mutations in EGFR, and fusions in NTRK, ROS1, and ALK genes led to profound improvements in clinical outcomes. The formation of chimeric proteins due to genomic rearrangements or at the post-transcriptional level is widespread and plays a critical role in tumor initiation and progression. Yet, the fusion landscape of lung cancer remains underexplored. Materials and Methods: We used the JAFFA pipeline to discover transcript fusions in early-stage non-small cell lung cancer (NSCLC). The set of detected fusions was further analyzed to identify recurrent events, genes with multiple partners and fusions with high predicted oncogenic potential. Finally, we used a generalized linear model (GLM) to establish statistical associations between fusion occurrences and clinicopathological variables. RNA sequencing was used to discover and characterize transcript fusions in 270 NSCLC samples selected from the Glans-Look specimen repository. The samples were obtained during the early stages of disease prior to the initiation of chemo- or radiotherapy. Results: We identified a set of 792 fusions where 751 were novel, and 33 were recurrent. Four of the 33 recurrent fusions were significantly associated with clinicopathological variables. Several of the fusion partners were represented by well-established oncogenes ERBB4, BRAF, FGFR2, and MET. Conclusion: The data presented in this study allow researchers to identify, select, and validate promising candidates for targeted clinical interventions.

The use of consolidative durvalumab following concurrent chemoradiotherapy in unresectable Stage III NSCLC patients has contributed to improvement in patient outcome; however, some patients experience early treatment failure on durvalumab, characterized by primary drug resistance or toxicity requiring durvalumab termination. With clinical characteristics associated with early treatment failure on immunotherapy not well explored, this study investigated this phenomenon and endeavored to identify predictors associated with resistance or toxicity on durvalumab.

Intracranial disease progression is a significant complication in patients with EGFR-positive non-small cell lung cancer (NSCLC) that can impact performance status, quality of life, and treatment options for patients. There is an increased need of oral tyrosine kinase inhibitors with central nervous system (CNS) activity in treating this population to prolong survival. Osimertinib is an oral tyrosine kinase inhibitor (TKI) which has demonstrated penetration of the blood brain barrier and effective treatment of intracranial metastases in some patients.

The phase-III FLAURA clinical trial demonstrated benefit and effectiveness of osimertinib as a first-line treatment for EGFR-mutant NSCLC patients; however, subgroup analysis suggests the magnitude of benefit may differ between Asian and non-Asian patients. Prior real-world data from our institution also suggests EGFR-mutant NSCLC patients of Asian racial ancestry are the most likely to derive benefit from earlier generation EGFR-inhibitors. This study examined real-world clinical population of EGFR-mutant patients treated with first-line osimertinib to compare and contrast the characteristics and response to osimertinib among Asian and non-Asian patients.

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.

In the absence of prospective studies to determine the best subsequent treatment after failure of first-line (1L) pembrolizumab in biomarker negative NSCLC, platinum doublet chemotherapy based on KEYNOTE-024 trial is preferred (ESMO guideline). This study examines the systemic treatment patterns and survival outcomes among immune checkpoint inhibitor (ICI) pretreated real-world NSCLC patients.

This is an update of an abstract entitled “The impact of sex on non-small cell lung cancer survival in Canada” that was presented at WCLC 2021. The leading cause of cancer-related death in Canada is lung cancer, with non-small cell lung cancer (NSCLC) accounting for the majority of lung cancer cases. Studies from other countries have demonstrated differences in NSCLC survival by sex, even after accounting for other factors. There has yet to be a robust analysis of the role of sex in NSCLC survival in the Canadian context.

Intracranial metastasis is a significant complication in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib is an oral tyrosine kinase inhibitor which has central nervous system (CNS) activity. However, many patients with intracranial metastases are treated with cranial radiation therapy (RT), which can have considerable toxicities. The optimal treatment for this patient population has not been elucidated. The purpose of this study was to assess CNS outcomes of real-world patients treated with Osimertinib +/- RT.

Immune checkpoint inhibitors (ICI) have good safety profile in NSCLC patients with poor performance status (PS) but understanding of their efficacy in this patient group is limited [PePS2, CheckMate 153 and 171 clinical trials]. Here, the authors evaluate survival outcomes with ICI treatment versus best supportive care (BSC) in ECOG PS 2 NSCLC patients (PS2). PS2 who were diagnosed or received first-line pembrolizumab ± chemotherapy (Pembro) in Alberta Canada between 2017-2021 were retrospectively analysed. Overall survival (OS) from diagnosis to death was evaluated and compared between Pembro and BSC group (i.e. received no systemic treatment) using Kaplan-Meier and multivariate analyses. EGFR, ROS1 and ALK positive patients were excluded. 54 PS2 were found, all were advanced NSCLC [50 non-squamous, 40 PD-L1 positive (>1%) and 33 KRAS mutant NSCLC]. The median (range) age was 69 (47-87) years. 67 % had at least 1 co-morbidity based on the Charlson's Comorbidity Index list. 67% received Pembro (monotherapy n=21), the median time to immune treatment was ∼56 days. Reason for no systemic treatment were died before treatment initiation n=3, patient declined or moved elsewhere n=3, unknown n=3, PS or declining health n=9. Pembro versus BSC group only differ by distant metastatic sites involvement, Pembro patients had less distant sites involvement [28 vs 61% M1c (AJCC TNM 8th), p=0.01] (Table). With median follow-up of 26 months, the median OS was 21 vs 2 months with Pembro and BSC (p<0.01) and was consistently better in Pembro patients among KRAS mutant patients (Table). In multivariate analysis, Pembro relative to BSC was associated with reduced risk of death [HR= 0.06, 95% CI: 0.02-0.18, p<0.01] after controlling for distant metastatic sites, age, co-morbidity, PD-L1 and KRAS status.Table: 45PECOG 2 NSCLC patients receiving first-line pembrolizumab ± chemotherapy (Pembro) vs. best supportive care (BSC)Survival outcomes in monthsBSC, n=18Pembro, n=36P value**Median overall survival (mOS)221<0.01mOS in KRAS mutant227<0.01mOS in PD-L1 ≥50%222<0.01mOS in PD-L1 1-49%29<0.01mOS in PD-L1 <1%390.04Clinical characteristics, n (%)Median body mass index (range), kg/m223 (16-42)26 (15-38)Age >70 years11 (61)13 (36)0.09Had at least 1 co-morbidity14 (78)22 (61)0.36>1 comorbidity6 (43)5 (23)0.27PD-L1 positive (>1%)12 (67)28 (78)0.08PD-L1 ≥50%5 (28)21 (58)0.08KRAS mutant13 (72)20 (56)0.13** Log Rank (Kaplan Meier Survival) and Fisher Exact (Descriptive statistics) Open table in a new tab ** Log Rank (Kaplan Meier Survival) and Fisher Exact (Descriptive statistics) Pembro compared to BSC offers survival advantage for PS2 NSCLC patients, even though reports show lower OS in PS2 when compared to good PS (ECOG 0-1) patients treated with ICI.

ROS1-rearranged non-small cell lung cancer (NSCLC), present in 1-2% of diagnoses, is a genetically distinct type of NSCLC which can be successfully managed through the use of targeted therapy, specifically the first-generation ALK-inhibitor, crizotinib, which doubles as highly effective inhibitor of aberrant ROS1 activity. Clinical trials have shown crizotinib to be safe and effective; however, the use of crizotinib and its safety and efficacy in real-world ROS1-rearranged populations requires further exploration.

The authors assessed the real-world effectiveness of newly approved regimen, atezolizumab plus carboplatin-etoposide (Atezo-CaE) for extensive stage (ES) small cell lung cancer (SCLC) in Alberta, Canada. Atezo-CaE is yet to be provincially funded for ES treatment but can be accessed through special access programs.

LIPI is a prognostic index which has demonstrated strong utility in metastatic NSCLC (mNSCLC) patients when treated with immune checkpoint inhibitors (ICIs). Recent pooled analysis using clinical trial data suggests that LIPI scores may also be prognostic of outcome in patients with mNSCLC treated with non-ICI systemic therapies such as tyrosine kinase inhibitors (TKIs) and cytotoxic chemotherapy (CTx). Recognizing both the increasing number of patients with mNSCLC who possess mutation-positive tumours and the potential differences between clinical trial and real-world patient populations, we sought to explore the prognostic ability of the LIPI among real-world mutation-positive mNSCLC patients in receipt of palliative-intent systemic therapy.

The Prognostic Nutritional Index (PNI) is an indicator of nutritional and immune status. Initially a prognostic index to evaluate the risk of recurrence and predict survival in patients following surgical procedures, recent studies have indicated the PNI may also have prognostic ability in non-resected lung cancer. The PNI has been shown to be independently predictive of outcome in patients with advanced/metastatic NSCLC (mNSCLC) treated with platinum-based chemotherapy (CTx). In response, this study explored the prognostic value of the PNI among real-world driver mutation-positive patients with mNSCLC receiving palliative intent systemic therapies, including (CTx), tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICI).

The COVID-19 pandemic has had significant secondary impacts on healthcare services worldwide, including delays to non-essential procedures and surgeries. Early efforts to reduce the spread of COVID-19 across Canada resulted in up to 45% fewer visits to family physicians and medical specialists between March and June of 2020 (National Physician Database, 2020, Canadian Institute for Health Information). In the context of cancer care, this may have resulted in fewer new cancer diagnoses as a consequence of limited access to a family physician or diagnositic services, and delayed time to surgery or treatment.

The impact of specific KRAS mutation on treatment outcomes remain unclear. We compared the association between systemic anti-cancer treatment (SACT) outcomes and specific KRAS mutations [G12C versus non-G12C mutants] in metastatic non-squamous NSCLC patients (mNSCLC).

INTRODUCTION:This study explored the use, safety, and efficacy of initial use of an ALK-inhibiting targeted therapy (ALK tyrosine kinase inhibitor [TKI]) in patients with ALK-rearranged NSCLC in a population-based, real-world clinical population within the province of Alberta, Canada.METHODS:Demographic, clinical, treatment, and outcome data of the patients with advanced or metastatic ALK-rearranged NSCLC receiving their first ALK TKI between 2014 and 2019 were included in the analysis.RESULTS:A total of 92 patients with ALK-rearranged NSCLC treated with ALK TKI (78% crizotinib, 22% alectinib) were identified. In the ALK-rearranged cohort, 1-year survival rate was 73% and median overall survival (OS) and progression-free survival (PFS) were 48.5 months and 17.0 months, respectively. An objective response rate of 49% was observed, and adverse events were reported in 70% of the patients, primarily of low grade (84%). Case-matched comparison to patients with ALK-wildtype disease treated with cytotoxic chemotherapy revealed the benefit of ALK TKI in the context of an ALK rearrangement (ALK-rearranged versus ALK-wildtype) (median post-treatment initiation OS: 46.8 versus 14.2 mo, p < 0.001). Outcomes, measured from the time of ALK TKI initiation, differed by Eastern Cooperative Oncology Group (ECOG) (ECOG < 2 versus ECOG ≥ 2) (median OS: not reached versus 6.8 mo, p < 0.001; median PFS 17.6 versus 7.4 mo, p = 0.02), disease presentation (relapsed versus de novo) (median PFS: 30.8 versus 15.0 mo, p = 0.04), and brain metastasis onset (brain metastases development during ALK TKI versus baseline brain metastases) (not reached versus 12.8 mo, p = 0.04).CONCLUSIONS:Clinical trials have firmly established that ALK TKIs are safe, well tolerated, and effective; these findings reveal that their impact in a real-world setting is just as profound. The availability and use of ALK TKI therapies contribute to the impressive gains in survival experienced by contemporary patients with ALK-rearranged disease, rendering patients with this oncodriven form of NSCLC among the longest surviving patients with lung cancer.

Lung cancer is the leading cause of cancer-related death in Canada. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, and while new treatments have been developed, survival outcomes remain poor. Literature from outside Canada indicates differences in NSCLC survival by sex. These differences cannot be explained by differences in stage, NSCLC subtype, age, or smoking history, indicating that sex may be an independent prognostic factor. The impact of sex on NSCLC survival has yet to be thoroughly examined in the Canadian context.