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Research

ROS1 mutation non-small cell lung cancer—access to optimal treatment and outcomes

29 Jan 2019
Amit Joshi, Nikhil Pande, Vanita Noronha, Vijay Patil, Rajiv Kumar, Anuradha Chougule, Trivedi Vaishakhi, Amit Janu, Abhishek Mahajan, Kumar Prabhash

Introduction: ROS1 oncogenic fusion, which was first identified by Rikova et al, is reported to be present in 1%–2% of non-small cell lung cancers (NSCLCs) and is defined as a distinct molecular sub-group. Crizotinib is very effective in ROS1-positive patients and is now Food and Drug Administration (FDA) approved for the treatment of patients with advanced ROS1-positive NSCLC. We report our experience in a tertiary cancer care hospital in India in ROS-1 positive patients.

Materials and method: The present series is a retrospective analysis of 22 patients from the prospectively maintained lung cancer audit. Demographic data were collected which included age, performance status, gender, stage, co-morbidities, sites of metastasis and smoking history. Data were also collected regarding the source of financing for crizotinib whether self-financed, through insurance or Non-Governmental Organisation (NGO) sponsored. Patients who had tested negative for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) and were subsequently found to be ROS1-mutation negative by fluorescence in situ hybridization (FISH) were evaluated on similar lines. All the data were entered and statistical analyses were performed using the SPSS software version 22.0.
Response evaluation was done by RECIST 1.1 criteria.

Results: Between January 2015 and December 2017, there were 22 patients who were ROS1 positive from a total of 535 patients in whom ROS1 testing was performed. A total of 16 patients could receive crizotinib and 6 patients were never exposed to crizotinib. Among the 16 patients who received crizotinib, 2 (12.5%) achieved complete response (CR) as their best response and continue to remain in CR at follow-up. 13 (81%) had a partial response as best response and of which on follow-up 5 (38%) have progressed, while 8 (62%) continue to maintain response. The patients who were on crizotinib had good tolerance with none experiencing any grade 3/4 toxicity. The median
follow-up of the entire cohort was 15.2 months in ROS1-positive cohort and 11.4 months in ROS1-negative cohort. In ROS1-positive cohort median, progression-free survival (PFS) was not reached and the estimated 2-year PFS was 54% and in ROS1-negative cohort, it was 5.1 months. The median overall survival of the entire ROS1-positive cohort was not reached and the estimated 1- and 2-year overall survival (OS) was 72% and 54%, respectively, and was 8.8 months in ROS1-negative cohort.

Conclusion: ROS1 rearrangement with an incidence of 4% of lung adenocarcinoma which is EGFR and ALK negative represents an important targetable driver mutation in the Indian population. Crizotinib also represents an effective treatment option with outcomes similar to those reported. Access to treatment remains an important roadblock to improve outcomes but innovative methods may improve access to these drugs.

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