ROS1 rearrangement positive...First-line therapy...Crizotinib

Crizotinib is recommended in the first-line setting in patients with stage IV NSCLC with ROS1 rearrangement, because it has shown results indicating improved response rate and duration of response [A¼ 100% and III, A].

...- Histologically or cytologically confirmed diagnosis of stage IV or incurable non-squamous non-small cell lung cancer with a documented ROS1 rearrangement (cohort 1) or MET-activating mutation (exon 14) (cohort 2) or MET-amplification (cohort 3) tested in either plasma or tissue, as applicable...

...Documented evidence of an ALK rearrangement (by FISH, IHC, or NGS), ROS1 rearrangement (by FISH or NGS), or MET oncogene as defined by MET exon 14 skipping (NGS), MET Y1003X mutation or MET gene fusion (NGS) in NSCLC tumor specimen by a CLIA-approved laboratory....

Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014-2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population….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.

...patients with advanced or metastatic ROS1-rearranged NSCLC, receiving crizotinib as their first targeted ROS1-inhibitor between January 2014 and June 2020 were identified….One-year survival was 47% following crizotinib initiation; median OS and PFS were 33.3 and 10.6 months, respectively. Disease control rate was 62%....This real-world study suggests crizotinib therapy for ROS1-rearranged NSCLC in a Canadian clinical setting is an effective, safe and tolerable therapy...

The median progression free survival (mPFS) after first-line crizotinib therapy was 23.0 months, and the median overall survival (mOS) was 60.0 months....First-line crizotinib treatment is beneficial in Chinese patients with ROS1-rearranged advanced NSCLC.

ROS1 status was determined by FISH or reverse transcriptase-polymerase chain reaction...Fifty-three patients received crizotinib, with a median duration of treatment of 22.4 months. At data cut-off, treatment was ongoing in 12 patients (23%). The objective response rate (ORR) was 72% [95% confidence interval (CI), 58% to 83%], including six confirmed complete responses and 32 confirmed partial responses; 10 patients had stable disease. Responses were durable (median duration of response 24.7 months; 95% CI, 15.2-45.3). ORRs were consistent across different patient subgroups. Median progression-free survival was 19.3 months (95% CI, 15.2-39.1).

Patients with pretreated advanced NSCLC and evidence of ROS1 rearrangements (cohort A) or MET deregulation (amplification, ratio MET/CEP7 >2.2 or MET exon 14 mutations, cohort B) were treated with crizotinib 250 mg twice daily orally...At data cutoff of September 2017, in cohort A, objective response rate was 65%, and median progression-free survival and overall survival were 22.8 months [95% confidence interval (CI) 15.2-30.3] and not reached, respectively. In cohort B, objective response rate was 27%, median progression-free survival was 4.4 months (95% CI 3.0-5.8), and overall survival was 5.4 months (95% CI, 4.2-6.5).

In this study, crizotinib showed marked antitumor activity in patients with advanced ROS1-rearranged NSCLC. ROS1 rearrangement defines a second molecular subgroup of NSCLC for which crizotinib is highly active.