11P ROS1-gene rearranged lung adenocarcinomas: Demographic, clinicopathologic and treatment profile in a cohort of Indian patients

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ROS1 translocations are seen in 1%-2% of non-small cell lung cancer (NSCLC) patients. There is limited data on the clinicopathologic profile of ROS1 translocated NSCLC. The study included 409 patients with NSCLC who were referred for molecular testing. Fluorescent in situ hybridisation (FISH) assays were performed to detect ROS1 gene rearrangements on 3-5μm tissue section from formalin-fixed-paraffin embedded (FFPE) tumor tissue. ZytoLight SPEC ROS1 Dual Color Break Apart FISH Probe (ZytoVision, Germany) was used. Clinicopathologic profiles of the FISH-positive patients were documented. Out of 409 cases of stage IV NSCLC, 18 (4.4%) cases were positive for a ROS1 gene rearrangement. Of the positive cases 11 were females and 7 were males. Smoking history was known for 11 patients of which 2 were smokers (all males) and 9 were non-smokers (7 females and 2 males). The median age was 49 years (range 28 - 65 years). The histopathology was adenocarcinoma in all cases with the solid subtype of adenocarcinoma being the most common histologic subtype (6 cases) followed by solid type with macronuclei (5 cases). Fifteen patients were treated with crizotinib of whom 4 received the drug in the first-line and 11 in the second-line. The overall response rate for crizotinib was 10/15 (66.6%) all of which were partial responses (PR). The disease control rate (PR + stable disease) was 14/15 (93.3%). One patient had disease progression on first-line crizotinib. The median duration of response was 9 months (range 1 to 19 months). After progression on crizotinib; immunotherapy with pembrolizumab was given in 3 patients with PD-L1 IHC of 13%, 65% and 5%. Peripheral edema was the most common toxicity with crizotinib and was reported in 6 (40%) of the patients. ROS-1 rearranged NSCLC represents 4% of all advanced stage NSCLC patients. Most patients were females, non-smokers and are diagnosed at a younger age (median 49years) compared to NSCLC with other driver mutations. Most patients present in an advanced stage. The response rates to crizotinib (most commonly used drug) is 66.6% with all of them being partial responses. Crizotinib is well tolerated in our cohort of patients.