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

Author(s): Caicun Zhou, M.D., Ph.D.¹; Laurent Greillier, M.D., Ph.D.²; Geoffrey Liu, M.D.³; Thomas John, M.B., B.S., Ph.D.⁴; Ligang Xing, M.D., Ph.D.⁵; Dariusz Kowalski, M.D., Ph.D.⁶; Regan M. Memmott, M.D., Ph.D.⁷; Ozan Yazici, M.D.⁸; Meili Sun, M.D.⁹; Catherine A. Shu, M.D.¹⁰; Elvire Pons-Tostivint, M.D., Ph.D.¹¹; Yun Fan, M.D.¹²; Gonzalo Fernandez-Hinojal, M.D., Ph.D.¹³; Elaine Shum, M.D.¹⁴; Mengzhao Wang, M.D.¹⁵; Federica Bertolini, M.D.¹⁶; D. Ross Camidge, M.D., Ph.D.¹⁷; Chengzhi Zhou, Ph.D.¹⁸; Ludovic Doucet, M.D.¹⁹; Qunying Hong, M.D.²⁰; Jian Fang, Ph.D.²¹; Dingzhi Huang, M.D.²²; Bo Jin, M.D.²³; Yan Yu, M.D., Ph.D.²⁴; Lorenzo Antonuzzo, M.D., Ph.D.²⁵; Denis Moro-Sibilot, M.D.²⁶; Jaafar Bennouna, M.D., Ph.D.²⁷; Gilberto de Castro, Jr., M.D., Ph.D.²⁸; Li Zheng, M.D., Ph.D.²⁹; John V. Heymach, M.D., Ph.D.³⁰; the WU-KONG28 Investigators*;

Source: DOI: 10.1056/NEJMoa2604461

Dr. Maen Hussein's Thoughts

Progression-free survival (PFS) was higher in the Sun group vs chemotherapy, 10.3 m vs 7.5 m with HR of .65 with higher responses (58.9% vs 31.1%) diarrhea high CK and anemia were the most common side effects. The issue is that amivan was not part of treatment and compared to chemotherapy ami in addition to chemotherapy had 11m PFS also in this trial few had brain mets so no evaluation for CNS protection or treatment. But an oral agent in patients who don’t want to come to the office often.

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

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

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.) Quick Take First-Line Sunvozertinib in EGFR Exon 20–Mutated NSCLC 2m 29s

Author Affiliations

¹Shanghai East Hospital, Shanghai; ²Assistance Publique–Hôpitaux de Marseille, Hôpital Nord, Marseille, France; ³Princess Margaret Cancer Centre, University Health Network, Toronto; ⁴Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; ⁵Shandong Cancer Hospital, Jinan, China; ⁶Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy, Klinika Nowotworow Pluca i Klatki Piersiowej, Warsaw, Poland; ⁷Ohio State University Brain and Spine Hospital, Columbus; ⁸Gazi University Faculty of Medicine Hospital, Ankara, Turkey; ⁹Central Hospital Affiliated to Shandong First Medical University, Jinan, China; ¹⁰Columbia University Medical Center, New York; ¹¹Centre Hospitalier Universitaire (CHU) de Nantes, Nantes, France; ¹²Zhejiang Cancer Hospital, Hangzhou, China; ¹³Clinica Universidad de Navarra, Madrid; ¹⁴Laura and Isaac Perlmutter Cancer Center NYU Langone Health, New York; ¹⁵Peking Union Medical College Hospital, Beijing; ¹⁶Oncology, Modena University Hospital, Modena, Italy; ¹⁷University of Colorado Hospital–Anschutz Cancer Pavilion (ACP), Aurora; ¹⁸First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; ¹⁹Institut de Cancérologie de L’Ouest, Nantes, France; ²⁰ZhongShan Hospital, Fudan University, Shanghai; ²¹Beijing Cancer Hospital, Beijing; ²²Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; ²³First Hospital of China Medical University, Shenyang; ²⁴Harbin Medical University Cancer Hospital, Harbin, China; ²⁵Azienda Ospedaliero Universitaria Careggi, Florence, Italy; ²⁶CHU Grenoble Alpes, Hôpital Albert Michallon, La Tronche, France; ²⁷Hôpital Foch, Suresnes, France; ²⁸Instituto do Cancer do Estado de São Paulo, São Paulo; ²⁹Dizal Pharmaceutical, Shanghai; ³⁰University of Texas M.D. Anderson Cancer Center, Houston

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