Although the prevalence of a cytogenetic abnormality in tumor biopsy is low, finding one or more abnormalities can expand the patient’s treatment options and create a more personalized regimen.
For example, Crizotinib is used to treat NSCLC patients that are positive for an EML4-ALK translocation and this is the molecular abnormality for which crizotinib received FDA approval. The drug’s manufacturer Pfizer created a FISH-based companion diagnostic tool to detect the abnormality and to ensure personalization.
In Bergerthon et al., one of the ROS1-positive NSCLC patients treated with crizotinib was presented as a case example. The patient was a 31-year-old male never-smoker diagnosed with multifocal bronchioloalveolar carcinoma in August 2010 and hypoxic. After being treated with erlotinib with no response, he was referred to Massachusetts General Hospital for further genetic testing.
Genetic testing revealed his tumor was ROS1-positive. He showed marked improvement less than one week after being started on crizotinib at the standard dose of 250mg twice daily. Two weeks after receiving his first dose, his hypoxia had resolved and, at eight weeks, his CT scans demonstrated nearly complete resolution of his tumor with no evidence of recurrence, suggesting that patients with ROS1-positive NSCLC are sensitive to therapeutic ROS1 inhibition by drugs such as crizotinib.
The case presented in Bergerthon et al. represented one patient examined in a 1,037-person study. In that study, the overall survival of ROS1-positive was not significantly different than ROS1-negative patients.
Also, Bergerthon et al. reported that NSCLC patients that are positive for ROS1 rearrangement are significantly younger than the average lung cancer patient (median age=49.8 years), have never smoked cigarettes, are predominantly males, and whose tumors are histologically adenocarcinoma. These clinicopathologic characteristics are very similar to those found in ALK-positive patients.
Furthermore, the authors suggested that these two genetic subtypes of NSCLC may share a common pathogenesis and possibly have similar environmental or genetic risk factors as well.
Our case study is very similar to that reported by Bergerthon et al. Although the prognosis of our patient’s case is unknown, crizotinib has thus far improved his overall functional status with radiographic evidence of disease regression, which is promising.
- Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012 Mar 10;30(8):863-70.