Crizotinib Therapy for Advanced Lung Adenocarcinoma and a ROS1 Rearrangement: Results From the EUROS1 Cohort

Abstract

Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1. Prospective clinical trials with crizotinib and other ROS1 inhibitors are ongoing or planned.

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

“…This recommendation is evidence based and supported by 9 studies, 30e38 6 of which informed on the association between ROS1 rearrangement and patient or tumor characteristics 30,31,34e37 and consisted of 1 prospective cohort study (PCS), 35 1 prospective-retrospective cohort study (PRCS), 31 and 4 retrospective cohort studies (RCSs). 30,34,36,37 The 3 remaining studies assessed clinical outcomes of patients treated with the ROS1-targeted therapy crizotinib 32,33,38 and included 1 nonrandomized clinical trial 33 and 3 RCSs. 32,38 All included studies were assessed for quality and none were found to have methodologic flaws that would raise concerns about the studies' findings (SDC Table 6).…”

“…30,34,36,37 The 3 remaining studies assessed clinical outcomes of patients treated with the ROS1-targeted therapy crizotinib 32,33,38 and included 1 nonrandomized clinical trial 33 and 3 RCSs. 32,38 All included studies were assessed for quality and none were found to have methodologic flaws that would raise concerns about the studies' findings (SDC Table 6). Refer to SDC Table 7 for a summary of findings from studies supporting the use of ROS1 molecular or cytogenetic testing to enable selection of patients for ROS1-targeted therapy.…”

“…A European multi-institutional retrospective study of 32 patients with ROS1-rearranged NSCLC treated with crizotinib demonstrated an 80% response rate and 9.1-month progression-free survival. 32 Overall survival for patients with ROS1-rearranged …”

Targeting oncogenic drivers in lung cancer: celebrating a decade of progress

“…Because of the high degree of homology between the kinase domains of ROS1 and ALK, and the potent inhibition of ROS1 kinase by crizotinib, the results were excellent and confirmed in the final report in 2014 [17]. This trial had an immediate impact on clinical practice, as demonstrated by the EUROS1 cohort study [18]. The ongoing EUCROSS trial is expected to produce further relevant data (NCT02183870), while other studies are focusing on acquired resistance and other ROS1 inhibitors to overcome crizotinib resistance [19].…”

Emerging uses of biomarkers in lung cancer management: molecular mechanisms of resistance

“…Patients with ROS proto-oncogene 1 RTK (ROS1) rearranged NSCLC in general respond to treatment with the ROS1 inhibitor-crizotinib very well with quite durable remissions being the norm, however these tumors eventually become resistant as well (76,77). There is limited data available on the mechanisms of acquired resistance to crizotinib in ROS1 positive NSCLC, however several secondary ROS1 mutations that can cause resistance have been identified, for example the G2026M mutation (gatekeeper) or the L2155S solvent-front (D2033N) mutation which can still respond to the multi-targeted TKI, cabozantinib which has ROS inhibitory activity as well (78)(79)(80).…”