Efficacy of Crizotinib among Different Types of ROS1 Fusion Partners in Patients with ROS1-Rearranged Non–Small Cell Lung Cancer

Abstract

These findings suggests that patients with CD74-ROS1 fusion partners are more likely to present with brain metastases. Although not independently significant, a trend toward improved survival was observed in patients in the non-CD74-ROS1 group when they were treated with crizotinib.

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

“…In fact, the clinical results are in complete agreement with those of other series. 4,24 Moreover, we used commercially available tools, so our findings could be replicated elsewhere.…”

“…Overall, the variety and prevalence of ROS1 partners identified were similar to those described. 24,37,45 The percentage of cases in which the suboptimal RNA quality and/or quantity resulted in low sequencing coverage highlights the need for an evidence-based algorithmic approach. 39,46,47 The fusion partner can influence both the IHC staining and the FISH pattern, with the EZR variant usually being associated with a membranous accentuation and isolated 3 0 signals, respectively.…”

“…9,13,40 Finally, our nonsignificant trend of better PFS for patients with the EZR-ROS1 fusion might be in alignment with the results of series in which almost every patient with an IGS achieved a complete response and with the recently published differential efficacy of crizotinib in the non-CD74-ROS1 group. 24,48 Unfortunately, this is still a controversial topic that would need larger multicenter series with longer follow-up and standardized NGS to draw definitive conclusions. 22,37 A review of published studies in the light of our findings suggests that there are two scenarios that can have important clinical consequences when ROS1 IHC is to be used as the primary screening method for ROS1 therapy: (1) a ROS1 FISH-false-positive result in a patient with another druggable alteration that is causing the ROS1 IHC positivity (awareness of the FISH potential pitfalls is essential [i.e., percentage of positive nuclei around the cutoff, 3 0 isolated pattern], and if the result is inconsistent, it is sensible to use a third methodology [i.e., NGS], which will potentially discover the reason for the IHC positivity) and (2) a ROS1 NGSnegative or failed report in a ROS1-rearranged sample that exhibited intense and homogeneous IHC staining.…”

Combined targeted DNA and RNA sequencing of advanced NSCLC in routine molecular diagnostics: Analysis of the first 3,000 Heidelberg cases

“…This is becoming increasingly important, because accumulating data suggest that several fusion variants have prognostic and predictive significance. 38 Hence, these patients could also presumably benefit from more stringent surveillance, for example with imaging studies or liquid biopsies. At our institution, we have recently retrospectively analyzed 67 EML4-ALK translocated NSCLC (overlap of n = 52 with the current cohort) using targeted NGS and found V3-driven tumors to have more metastatic sites at diagnosis and shorter OS compared to V1-and V2-driven tumors due to earlier failure of all main treatment modalities, i.e.…”

“…Similar seems to hold true for ROS1 + NSCLC, as CD74-ROS1 patients are more likely than patients with other ROS1 fusions to develop brain metastases, which go along with poor prognosis. 38 Hence, these patients could also presumably benefit from more stringent surveillance, for example with imaging studies or liquid biopsies.…”