Caicun Zhou, Laurent Greillier, Geoffrey Liu, Thomas John, Ligang Xing, Dariusz Kowalski, Regan M. Memmott, Ozan Yazici, Meili Sun, Catherine Shu, Elvire Pons-Tostivint, Yun Fan, Gonzalo Fernandez-Hinojal, Elaine Shum, Mengzhao Wang, Federica Bertolini, D. Ross Camidge, Chengzhi Zhou, Ludovic Doucet, 洪群英, Jian Fang, Dingzhi Huang, Bo Jin, Yan Yu, L Antonuzzo, Denis Moro-Sibilot, Jaafar Bennouna, Gilberto de Castro, Li Zheng, J Heymach
BACKGROUND: ) exon 20 insertion mutations. Data are needed on the efficacy and safety of sunvozertinib as a first-line treatment for NSCLC. METHODS: exon 20 insertions to receive sunvozertinib or chemotherapy (carboplatin-pemetrexed). The primary end point was progression-free survival as assessed by blinded independent central review. Crossover to the sunvozertinib group was allowed after disease progression was confirmed. Secondary end points included overall survival, investigator-assessed progression-free survival, objective response (complete or partial response), change in tumor size, and duration of response. RESULTS: A total of 324 patients were randomly assigned to receive sunvozertinib (163 patients) or chemotherapy (161 patients). Treatment with sunvozertinib led to significantly longer median progression-free survival than chemotherapy (10.3 vs. 7.5 months; hazard ratio for disease progression or death, 0.65; 95% confidence interval, 0.50 to 0.85; P<0.001). At 12 months, progression-free survival was reported in 46.1% of the patients in the sunvozertinib group and in 26.7% of those in the chemotherapy group; the data for overall survival were immature (38.9% maturity). The percentage of patients with an objective response was 58.9% in the sunvozertinib group and 31.1% in the chemotherapy group; the median best percentage change in tumor size was -42.1% and -24.7% respectively, and the median duration of response was 11.2 and 7.1 months. Grade 3 or higher adverse events were reported in 75.5% of the patients in the sunvozertinib group and in 56.7% of those in the chemotherapy group. In the sunvozertinib group, the most common adverse events of grade 3 or higher included increased serum creatine kinase levels, diarrhea, and anemia. No deaths were attributed to adverse events considered by the investigators to be related to sunvozertinib. CONCLUSIONS: exon 20 insertions. (Funded by Dizal Pharmaceuticals; WU-KONG28 ClinicalTrials.gov number, NCT05668988.).