Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings
Introduction Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy.Methods This open-label,...
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BMJ Publishing Group
2024-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/12/e009301.full |
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| author | Benjamin Izar Justin F Gainor Mark M Awad Codruta Chiuzan Anjali Saqi Catherine A Shu Katja Schulze Brian S Henick Naiyer A Rizvi Samyukta Mallick Yohanna Georgis Peter D Koch Stephanie Izard Robert F Garofano Cheryl V Wong Jessica Grindheim Joshua R Sonett Alison M Taylor |
| author_facet | Benjamin Izar Justin F Gainor Mark M Awad Codruta Chiuzan Anjali Saqi Catherine A Shu Katja Schulze Brian S Henick Naiyer A Rizvi Samyukta Mallick Yohanna Georgis Peter D Koch Stephanie Izard Robert F Garofano Cheryl V Wong Jessica Grindheim Joshua R Sonett Alison M Taylor |
| author_sort | Benjamin Izar |
| collection | DOAJ |
| description | Introduction Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy.Methods This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery. Major pathological response (MPR, primary endpoint) was previously reported; here, we report 3-year disease-free survival (DFS), OS, and clinical characteristics of patients developing brain metastases (BM) with integrated data from tumor genomics, gene expression, and quantitative immunofluorescent measurement of immune markers.Results Of 30 enrolled patients, 29 were taken to the operating room. 26 underwent R0 resection, with 17 experiencing MPR (10 pCR). With a median follow-up of 39.5 months, the median OS was 55.8 months, and the median DFS was 34.5 months. Landmark OS at 36 months was 77%. Among 14 patients with recurrent disease, 6 patients had BM. Patients whose tumors had mutations in STK11 and KEAP1 did not have a significantly higher incidence of BM. Reduced copy number of STK11 and KEAP1, both residing on chromosome 19p, was observed in ~1/3 of tumors. Reduced CN of STK11 was significantly associated with worse pathological response and incidence of BM.Conclusions Consistent with recent phase III studies, 3-year OS data with neoadjuvant atezolizumab+chemotherapy was associated with prolonged PFS and OS. Establishing associations between STK11 and KEAP1 genomic alterations and key clinical outcomes in early-stage NSCLC requires further study. |
| format | Article |
| id | doaj-art-77e20eae4a3e4e62aad64ae34421fa1b |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-77e20eae4a3e4e62aad64ae34421fa1b2025-01-13T15:50:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-12-01121210.1136/jitc-2024-009301Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findingsBenjamin Izar0Justin F Gainor1Mark M Awad2Codruta Chiuzan3Anjali Saqi4Catherine A Shu5Katja Schulze6Brian S Henick7Naiyer A Rizvi8Samyukta Mallick9Yohanna Georgis10Peter D Koch11Stephanie Izard12Robert F Garofano13Cheryl V Wong14Jessica Grindheim15Joshua R Sonett16Alison M Taylor17Department of Medicine, Division of Hematology and Medical Oncology, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, New York, New York, USADepartment of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USADepartment of Hematology/Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USADepartment of Biostatistics, Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, USADepartment of Medicine, Division of Hematology and Medical Oncology, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, New York, New York, USADepartment of Medicine, Division of Hematology and Medical Oncology, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, New York, New York, USADepartment of Biomarker Development and Medical Affairs, Genentech-Roche, San Francisco, California, USADepartment of Medicine, Division of Hematology and Medical Oncology, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, New York, New York, USADepartment of Medicine, Division of Hematology and Medical Oncology, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, New York, New York, USAPathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USAPathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USAPathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USADepartment of Biostatistics, Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, USADepartment of Medicine, Division of Hematology and Medical Oncology, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, New York, New York, USADepartment of Biomarker Development and Medical Affairs, Genentech-Roche, San Francisco, California, USADepartment of Biomarker Development and Medical Affairs, Genentech-Roche, San Francisco, California, USADepartment of Surgery, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, New York, New York, USAPathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USAIntroduction Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy.Methods This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery. Major pathological response (MPR, primary endpoint) was previously reported; here, we report 3-year disease-free survival (DFS), OS, and clinical characteristics of patients developing brain metastases (BM) with integrated data from tumor genomics, gene expression, and quantitative immunofluorescent measurement of immune markers.Results Of 30 enrolled patients, 29 were taken to the operating room. 26 underwent R0 resection, with 17 experiencing MPR (10 pCR). With a median follow-up of 39.5 months, the median OS was 55.8 months, and the median DFS was 34.5 months. Landmark OS at 36 months was 77%. Among 14 patients with recurrent disease, 6 patients had BM. Patients whose tumors had mutations in STK11 and KEAP1 did not have a significantly higher incidence of BM. Reduced copy number of STK11 and KEAP1, both residing on chromosome 19p, was observed in ~1/3 of tumors. Reduced CN of STK11 was significantly associated with worse pathological response and incidence of BM.Conclusions Consistent with recent phase III studies, 3-year OS data with neoadjuvant atezolizumab+chemotherapy was associated with prolonged PFS and OS. Establishing associations between STK11 and KEAP1 genomic alterations and key clinical outcomes in early-stage NSCLC requires further study.https://jitc.bmj.com/content/12/12/e009301.full |
| spellingShingle | Benjamin Izar Justin F Gainor Mark M Awad Codruta Chiuzan Anjali Saqi Catherine A Shu Katja Schulze Brian S Henick Naiyer A Rizvi Samyukta Mallick Yohanna Georgis Peter D Koch Stephanie Izard Robert F Garofano Cheryl V Wong Jessica Grindheim Joshua R Sonett Alison M Taylor Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings Journal for ImmunoTherapy of Cancer |
| title | Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings |
| title_full | Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings |
| title_fullStr | Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings |
| title_full_unstemmed | Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings |
| title_short | Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings |
| title_sort | neoadjuvant atezolizumab chemotherapy for resectable nsclc 3 year clinical update of phase ii clinical trial results and translational findings |
| url | https://jitc.bmj.com/content/12/12/e009301.full |
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