Treatment Patterns and Survival in Patients with ALK-Positive Non-small-Cell Lung Cancer: A Canadian Retrospective Study

Kayaniyil, Sheena; Hurry, M.; Wilson, Jonathan; Wheatley‐Price, Paul; Melosky, Barbara; Rothenstein, J.; Cohen, Victor; Koch, Caroline; Zhang, J; Osenenko, Katherine M.; Liu, Geoffrey

doi:10.3747/co.23.3273

Cited by 19 publications

(22 citation statements)

References 9 publications

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“…Prior work suggested that males and females have similar PFS benefit from ALKIs, whereas the data on differences in OS by sex have been conflicting. 1,6,[13][14][15][16][17][18][19] Crizotinib is known to decrease free testosterone in males; however, although our site was active in discovering this, only 60% of males began taking crizotinib at UCCC. 20 Consequently, whether all male patients were screened and/or treated for low testosterone and the consequences of such treatment remain unknown.…”

Section: Discussionmentioning

confidence: 94%

Natural History and Factors Associated with Overall Survival in Stage IV ALK-Rearranged Non–Small Cell Lung Cancer

Pacheco

Gao

Smith

et al. 2019

Journal of Thoracic Oncology

109

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Introduction: Clinical variables describing the natural history and longitudinal therapy outcomes of stage IV anaplastic lymphoma kinase gene rearrangement positive (ALK-positive) NSCLC and their relationship with long-term overall survival (OS) have not previously been described in detail. Methods: Patients with stage IV NSCLC treated with an ALK inhibitor at the University of Colorado Cancer Center from 2009 through November 2017 were identified retrospectively. OS curves were constructed by using Kaplan-Meier methods. Multivariate Cox proportional hazard analysis was used to determine the relationship of variables with OS. Results: Of the 110 patients with ALK-positive NSCLC who were identified, 105 received crizotinib as their initial ALK inhibitor. With a median follow-up time of 47 months, the median OS time from diagnosis of stage IV disease was 81 months (6.8 years). Brain metastases at diagnosis of stage IV disease (hazard ratio ¼ 1.01, p ¼ 0.971) and year of stage IV presentation (p ¼ 0.887) did not influence OS. More organs with tumor at diagnosis of stage IV disease was associated with worse OS (HR ¼ 1.49 for each additional organ with disease, including the CNS [p ¼ 0.002]). Each additional month of pemetrexed-based therapy was associated with a 7% relative decrease in risk of death. Conclusion: Patients with stage IV ALK-positive NSCLC can have prolonged OS. Brain metastases at diagnosis of stage IV disease does not influence OS. Having more organs involved with tumor at stage IV presentation is associated with worse outcomes. Prolonged benefit from pemetrexed is associated with better outcomes.

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Section: Discussionmentioning

confidence: 94%

Natural History and Factors Associated with Overall Survival in Stage IV ALK-Rearranged Non–Small Cell Lung Cancer

Pacheco

Gao

Smith

et al. 2019

Journal of Thoracic Oncology

109

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“…This is particularly relevant when taking into consideration that clinical trials have a stern patient selection and thus underrepresented populations might respond differently to proposed therapy. Real-world clinical practice data on the use of crizotinib have been documented for patients in Canada [16] and China [17], and recently a large series reported on several European Union countries [18]. However, the experience in the Latin American population has been scarcely discussed [19, 20].…”

Section: Introductionmentioning

confidence: 99%

Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices

et al. 2018

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Objective: This study describes the real-world characteristics, treatment sequencing, and outcomes among Hispanic patients with locally advanced/metastatic ALK-positive non-small-cell lung cancer (NSCLC) treated with crizotinib. Methods: A retrospective patient review was conducted for several centers in Latin America. Clinicians identified ALK-positive NSCLC patients who received crizotinib and reported their clinical characteristics, treatments, and survival. Overall survival and progression-free survival (PFS) were described. A Random Forest Tree (RFT) model was constructed to predict brain progression. Results: A total of 73 patients were included; median age at diagnosis was 58 years, 60.3% were female, and 93.2% had adenocarcinoma. Eighty-nine percent of patients were never smokers/former smokers, 71.1% had ≥2 sites of metastasis, and 20.5% had brain metastases at diagnosis. The median PFS on first-line crizotinib was 7.07 months (95% CI 3.77–12.37) and the overall response rate was 52%. Of those who discontinued crizotinib, 55.9% progressed in the central nervous system (CNS). The RFT model reached a sensitivity of 100% and a specificity of 88% for prediction of CNS progression. Conclusions: The overall response rate and the PFS observed in Hispanic patients with ALK-positive NSCLC treated with first-line crizotinib were similar to those in previous reports. An RFT model is helpful in predicting CNS progression and can help clinicians tailor treatments in a resource-limited practice.

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“…A total of 38 publications assessed outcomes of use of an ALK inhibitor after an initial ALK inhibitor. Of the 38 publications, 25 were from clinical trials35–37,40–42,61–79 and 13 were from observational studies 44–48,50,54,57,80–84. All 38 publications reported on use of a second-generation ALK inhibitor after initial crizotinib therapy; one publication of an observational study also included a population that used a second-generation ALK inhibitor after an initial second-generation ALK inhibitor (ceritinib after initial alectinib),47 and one publication of an observational study mentioned two patients who received crizotinib after alectinib 84.…”

Section: Resultsmentioning

confidence: 99%

<p>Systematic review of sequencing of ALK inhibitors in <em>ALK</em>-positive non-small-cell lung cancer</p>

Barrows¹,

Wright²,

Copley-Merriman³

et al. 2019

LCTT

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The objective of this study was to understand outcomes of patients treated with ALK inhibitors, especially when ALK inhibitors are followed by other ALK inhibitors. A systematic literature review was conducted in PubMed, Embase, and Cochrane through July 17, 2017. Conference abstracts (three meetings in past 2 years) also were searched. Of 504 unique publications, 80 met inclusion criteria (47 clinical trials, 33 observational studies). Observational studies have the potential to provide information for ALK inhibitors used sequentially. Ten observational studies reported median overall survival of crizotinib-led sequences ranging from 30.3 to 63.75 months from initiation of crizotinib; 49.4-89.6 months from metastatic non-smallcell lung cancer diagnosis; and 15.5-22.0 months from initiation of the second-generation ALK inhibitor after initial crizotinib. Sequencing of ALK inhibitors may benefit patients progressing on initial ALK inhibitors.

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Treatment Patterns and Survival in Patients with ALK-Positive Non-small-Cell Lung Cancer: A Canadian Retrospective Study

Abstract: Background Crizotinib was the first agent approved for the treatment of anaplastic lymphoma kinase (ALK)-

Cited by 19 publications

References 9 publications

Natural History and Factors Associated with Overall Survival in Stage IV ALK-Rearranged Non–Small Cell Lung Cancer

Natural History and Factors Associated with Overall Survival in Stage IV ALK-Rearranged Non–Small Cell Lung Cancer

Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices

<p>Systematic review of sequencing of ALK inhibitors in <em>ALK</em>-positive non-small-cell lung cancer</p>

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