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. 2022 Mar 14;29(3):1967-1982.
doi: 10.3390/curroncol29030160.

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

Amanda J W Gibson  1 , Adrian Box  1   2 , Winson Y Cheung  1   3 , Michelle L Dean  1 , Anifat A Elegbede  1 , Desiree Hao  1   3 , Aliyah Pabani  1   3 , Randeep Sangha  4   5 , Dafydd Gwyn Bebb  1   3
Affiliations

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

Amanda J W Gibson et al. Curr Oncol. .

Abstract

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.

Keywords: ROS1-rearranged NSCLC; biomarker testing; crizotinib; metastatic disease; real-world outcomes; targeted therapy.

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Conflict of interest statement

This study received funding from a Pfizer Global Medical Grant (ID# 63468363_. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Outside of the scope of this study, D.G.B received payment from Pfizer for participation in Pfizer advisory boards. A.B. has received honoraria for lectures from AstraZeneca and Precision Rx-Dx Inc. R.S. has received personal fees from Pfizer, Boehringer-Ingelheim, AstraZeneca, Roche/Genentech, Bristol Myers Squibb, Merck, Novartis, AbbVie, Takeda and TEVA outside the submitted work. A.P. has received honoraria for lectures from AstraZeneca, Pfizer, Roche and Bristol Myers Squibb, and participated in advisory boards for AstraZeneca and Bristol Myer Squibb, and consultancy fees from the Canadian Agency for Drugs and Technologies in Health. D.H. has received funding for local conference support club from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Merck, Pfizer, Roche and Takeda, reports honoraria for advisory board participation and clinical trial funding from AstraZeneca, Bristol Myer Squibb, Boehringer Ingelheim, Takada, Eli Lilly and Purdue. W.Y.C. has no conflicts to disclose.

Figures

Figure 1
Figure 1
Alberta vs. clinical trial vs. real-world cohorts. Median overall survival on crizotinib (a); median progression-free survival on crizotinib (b).
Figure 2
Figure 2
Clinical response to crizotinib: one-year survival (a); clinical response to crizotinib and time to crizotinib initiation (b); impact of M-stage on clinical response to crizotinib (c); impact of M-stage to time to progression on crizotinib (d).
Figure 3
Figure 3
Brain metastases and crizotinib: presence/absence of brain metastases and impact on mOS (a); impact of brain metastasis at time of crizotinib initiation and impact on mPFS (b); demographic and clinical response differences of patients with/without brain metastases at crizotinib initiation (c).
See this image and copyright information in PMC

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