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Publications

Journal Article Ahead of print

PubMed: 42212913 DOI: 10.1056/NEJMoa2604461

First-Line Sunvozertinib in NSCLC with EGFR Exon 20 Insertion Mutations.

N Engl J Med

Authors: 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, Qunying Hong, Jian Fang, Dingzhi Huang, Bo Jin, Yan Yu, Lorenzo Antonuzzo, Denis Moro-Sibilot, Jaafar Bennouna, Gilberto de Castro, Li Zheng, John V Heymach

Affiliations

  • Shanghai East Hospital, Shanghai.
  • Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France.
  • Princess Margaret Cancer Centre, University Health Network, Toronto.
  • Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
  • Shandong Cancer Hospital, Jinan, China.
  • Narodowy Instytut Onkologii im. Marii SkÅ‚odowskiej-Curie PaÅ„stwowy Instytut Badawczy, Klinika Nowotworow Pluca i Klatki Piersiowej, Warsaw, Poland.
  • Ohio State University Brain and Spine Hospital, Columbus.
  • Gazi University Faculty of Medicine Hospital, Ankara, Turkey.
  • Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • Columbia University Medical Center, New York.
  • Centre Hospitalier Universitaire (CHU) de Nantes, Nantes, France.
  • Zhejiang Cancer Hospital, Hangzhou, China.
  • Clinica Universidad de Navarra, Madrid.
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health, New York.
  • Peking Union Medical College Hospital, Beijing.
  • Oncology, Modena University Hospital, Modena, Italy.
  • University of Colorado Hospital-Anschutz Cancer Pavilion (ACP), Aurora.
  • First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Institut de Cancérologie de L'Ouest, Nantes, France.
  • ZhongShan Hospital, Fudan University, Shanghai.
  • Beijing Cancer Hospital, Beijing.
  • Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • First Hospital of China Medical University, Shenyang.
  • Harbin Medical University Cancer Hospital, Harbin, China.
  • Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
  • CHU Grenoble Alpes, Hôpital Albert Michallon, La Tronche, France.
  • Hôpital Foch, Suresnes, France.
  • Instituto do Cancer do Estado de São Paulo, São Paulo.
  • Dizal Pharmaceutical, Shanghai.
  • University of Texas M.D. Anderson Cancer Center, Houston.

Abstract

BACKGROUND

Sunvozertinib received accelerated approval for use in later lines of therapy for patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Data are needed on the efficacy and safety of sunvozertinib as a first-line treatment for NSCLC.

METHODS

In this phase 3, international trial, we randomly assigned, in a 1:1 ratio, patients with advanced nonsquamous NSCLC with EGFR 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

The efficacy of sunvozertinib was superior to that of chemotherapy as first-line treatment for advanced NSCLC with EGFR exon 20 insertions. (Funded by Dizal Pharmaceuticals; WU-KONG28 ClinicalTrials.gov number, NCT05668988.).

MeSH

Progression-Free Survival, Neoplasms, Disease Progression, Carcinoma, Non-Small-Cell Lung, Drug Therapy, Drug-Related Side Effects And Adverse Reactions, Exons, Therapeutics, Mutation, Chemotherapy