Lung adenocarcinoma patients with ROS1-rearranged tumors by sex and smoking intensity
Yanmei Peng,
Vinicius Ernani,
Dan Liu,
Qian Guo,
Markay Hopps,
Joseph C. Cappelleri,
Ruchi Gupta,
Mariza de Andrade,
Jun Chen,
Eunhee S. Yi,
Ping Yang
Affiliations
Yanmei Peng
Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, AZ, 85259, USA; Department of Oncology, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, 102400, China
Vinicius Ernani
Division of Hematology and Medical Oncology, Department of Medicine, Mayo Clinic, AZ, 85054, USA
Dan Liu
Division of Pulmonary & Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610064, China; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, AZ, 85259, USA
Qian Guo
Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, AZ, 85259, USA
Markay Hopps
Vaccine R&D, Pfizer Inc, New York, NY, 10017, USA
Joseph C. Cappelleri
Executive Director of Biostatistics, Pfizer Inc, Groton, CT, 06340, USA
Ruchi Gupta
Division of Biostatistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA
Mariza de Andrade
Division of Biostatistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA
Jun Chen
The Second Affiliated Hospital of Dalian Medical University, Shahekou District, Dalian, 116023, China; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, AZ, 85259, USA
Eunhee S. Yi
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA
Ping Yang
Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, AZ, 85259, USA; Corresponding author.
Background: ROS1 rearrangements (ROS1+) define a distinct molecular subset of lung adenocarcinomas. ROS1 + tumors are known to occur more in never-smokers, but the frequency and outcome of ROS1 positivity by sex and smoking intensity are not clearly documented. Patients and methods: This patient cohort study included all never- (<100 cigarettes lifetime) and light- (100 cigarettes-20 pack-years) smokers, and a sample of heavy-smokers. ROS1 + rates by sex and smoking intensity were compared within and beyond our study. Survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards models. Results: Of the 571 total patients, ROS1 + was detected in 24 (4.2%): 6.4% in men and 3.0% in women; 5.1% in never-, 5.7% in light-, and 1.8% in heavy-smokers (P=0.05). Among the 209 stage IIIB-IV patients, men had much higher ROS1 + rate (11.1%) not only than women (1.7%, P=0.004) in our study, but also than men (0.4%–1.8%) in 8 published studies (Ps = 0.0019–0.0001). ROS1+ rates were similar between never- (9.3%) and light-smokers (8.1%) and significantly lower in heavy-smokers (1.2%, P=0.017), a finding confirmed by 6 published studies (Ps = 0.041–0.0001). Overall survival of ROS1 + patients were significantly better than the ROS1- (P=0.023) mainly due to targeted therapy. Among patients who exhibited resistance to crizotinib, follow-up treatment of entrectinib and lorlatinib showed remarkable survival benefits. Conclusions: The ROS1 + rates were higher in men than in women, and similar in never- and light-smokers, more pronounced in stage IIIB-IV patients. Newer-generation ALK/ROS1-targeted drugs showed efficacy in a cohort of crizotinib resistant ROS1 + patients. These results, when validated, could assist efficiently accruing ROS1 + patients.
