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NSCLC driver mutations in the Quebec population: Epidemiologic and clinical evaluation.
Abstract
e22159
Background: Recent advances in lung cancer treatment embrace the recognition of molecular pathways implicated in its pathogenicity, paving the path to personalized therapies. We conducted a retrospective analysis to characterize the molecular features of the population treated for non-squamous non-small cell lung cancer (NS-NSCLC) in the province of Quebec. Methods: 622 patients with NS-NSCLC and adequate tumor blocks, treated at the CHUM between 2006 and 2008, were included. All samples were tested for ALK translocations (by IHC and FISH), EGFR classical exon 19 and 21 mutations by PCR (fragment analysis and qPCR) and for KRAS codon 12 and 13 mutations by mismatch PCR-RFLP. Molecular features were matched to demographic characteristics and clinical outcomes. Results: So far, complete results are available for 153 patients. Considering the amount of tumor tissue available, this population is largely represented by patients with local or loco-regional disease (n= 140, 91.5%). A minority of patients (10.3%) was never or light smokers (< 10 pack-yrs). Only 2 patients (1.3%) were of Asian descent. The following table depicts the outcomes of this cohort of patients segregated according to mutation status and extent of disease. Conclusions: ALK rearrangements were not identified in this unselected NS-NSCLC population characterized by localized disease and strong smoking history. ALK translocation prevalence in different populations is likely to be largely influenced by its tumor stage distribution, tobacco exposure and the use of selection criteria for molecular testing. An expanded cohort of patients will be presented at the meeting. [Table: see text]
... In addition to providing insight into the drivers of treatment decisions, our results also provide some context for the current epidemiology of lung cancer in Quebec, which appears to be comparable to that in the reported literature in terms of median age at diagnosis, incidence by sex, and distribution by histologic subtype, with adenocarcinoma being the most common histolog y, followed by squamous cell carcinoma and sclc 2 . Rates of EGFR mutation and ALK gene rearrangement were less than those reported in other white populations, but our results are congruent with descriptive data from a recent Canadian cohort [33][34][35] . ...
Purpose:
Despite numerous breakthrough therapies, inoperable lung cancer still places a heavy burden on patients who might not be candidates for chemotherapy. To identify potential candidates for the newly emerging immunotherapy-based treatment paradigms, we explored the clinical and biologic factors affecting treatment decisions.
Methods:
We retrospectively reviewed the records of patients diagnosed at our university-affiliated cancer centre between 1 January 2011 and 31 December 2013. Patient demographics, systemic treatment, and survival were examined.
Results:
During the 3-year study period, 683 patients fitting the inclusion criteria were identified. First-line therapy was administered in 49.5% of patients; only 22.4% received further lines of therapy. The main reasons for withholding therapy were poor performance status [ps (43.2%)], rapidly deteriorating ps (31.9%), patient refusal of therapy (20.9%), and associated comorbidities (4%). Older age, the presence of brain metastasis at diagnosis, and non-small-cell histology were also associated with therapeutic restraint. Oncology referrals were infrequent in patients who did not receive therapy (32.2%). Older patients and those with a poor ps experienced superior survival when treatment was administered (hazard ratio: 0.25; 95% confidence interval: 0.16 to 0.38; and hazard ratio: 0.44; 95% confidence interval: 0.23 to 0.87 respectively; p < 0.001).
Conclusions:
Advanced lung cancer still poses a therapeutic challenge, with a high proportion of patients being deemed unfit for therapy. This issue cannot be resolved until appropriate measures are taken to ensure the inclusion of older patients and those with a relatively poor ps in large clinical trials. Immunotherapy might be interesting in this setting, given that it appears to be more tolerable. Another consequential undertaking would be the deployment of strategies to reduce wait times during the diagnostic process for patients with a high index of suspicion for lung cancer.
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