183. Surgical Outcomes in AFT-46: CHIO3: CHemotherapy Combined with Immune Checkpoint Inhibitor for Operable Stage IIIA/B Non-Small Cell Lung Cancer

OBJECTIVE: Enthusiasm for resection of Stage III (N2) NSCLC has increased given impressive outcomes with neoadjuvant or perioperative chemotherapy and checkpoint inhibitors (CPI). Surgery for Stage III NSCLC is more complex and carries higher risk. The addition of CPI's creates an uncertain landscape with hilar fibrosis and more difficult dissection. The primary endpoint of AFT-46, N2 nodal clearance (N2NC) exceeding the goal of 50% (22/31, 71%), has previously been reported. We describe herein surgical outcomes from this N2+ NSCLC cohort following chemotherapy and durvalumab.
METHODs: This was an open-label, single arm phase 2 NCI cooperative group trial enrolled at 9 US hospitals. Eligible patients had resectable stage III NSCLC, pathologically proven N2+. Patients received 4 cycles of platinum doublet + durvalumab followed by lobectomy or greater, and adjuvant durvalumab Q4 weeks for 1 year. Surgical approach, extent of resection, extent of lymphadenectomy, morbidity, mortality, time intervals between treatment steps, and receipt of adjuvant therapy were analyzed.
RESULTS: From 2021-2023, 38 patients were enrolled; 31 patients underwent resection (81.6%). DSMB recommended early closure as primary endpoint had been met on interim analysis. Surgical outcomes (Table) are notable for R0 resection in 29/31 patients (93.5%), low pneumonectomy rate (2/31, 6.5%) median LOS 3 d, no mortality at 30 and 90 d. Minimally invasive strategy was possible in 19/31 (61%; 2 VATS, 17 robotic), with 3 nonurgent conversions (3/22, 13.6%) to thoracotomy (total open: 12/31, 39%). Hilar fibrosis, or challenging dissection, was mentioned in 15/31 (48.4%) operative notes, but no patient required sleeve resections, vascular repair, nor circulatory support. Median interval from neoadjuvant therapy to surgery was 6.5 weeks, and from surgery to adjuvant therapy was 5.5 weeks. All 23 patients recommended to receive adjuvant therapy were able to do so.
CONCLUSION: This is the first report of surgical outcomes in an exclusively N2+ population following chemotherapy and CPI. Surgery in Stage III (N2) NSCLC after neoadjuvant durvalumab plus chemotherapy on AFT46 was accomplished with no mortality, high rates of minimally invasive surgery, compete resection, and lobectomy, with prompt return to oncologic therapy. Resection as part of a multidisciplinary strategy for N2+ NSCLC can be achieved with excellent surgical outcomes and does not interfere with receipt of systemic therapy.

Linda Martin (1), Xiaofei Wang (2), David Kozono (3), James Urbanic (4), Ankit Bharat (5), Mark Crye (6), Mark Ferguson (7), Samuel Kim (8), Edward Todd Robbins (9), Jason Wallen (6), Thomas Stinchcombe (10), Jyoti Patel (11), (1) University of Virginia Health System, Charlottesville, VA, (2) N/A, United States, (3) Dana-Farber Cancer Institute, Boston, MA, (4) UCSD Radiation Oncology, La Jolla, CA, (5) Northwestern University Feinberg School of Medicine, Chicago, IL, (6) N/A, Syracuse, NY, (7) University of Chicago, Chicago, IL, (8) Northwestern University Feinberg School of Medicine, Wilmette, IL, (9) Baptist Memorial Hospital, Memphis, TN, (10) Duke University Medical Center, Sainte-Anne-Des-Lacs, QC, (11) Northwestern University, Chicago, IL

Stephen Broderick

Commentator

Dr. Stephen R. Broderick MD, MPHS is a thoracic surgeon at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and Sibley Memorial Hospital.  After graduation from the Georgetown University School of Medicine he completed a residency in general surgery at the Weill Cornell New York Presbyterian Hospital.  During residency he dedicated two years to thoracic oncology research at Memorial Sloan Kettering Cancer Center.  His work at MSKCC focused on DNA copy number and gene expression changes in lung adenocarcinoma and was included in The Cancer Genome Atlas.  Following residency he completed a fellowship in cardiothoracic surgery at Washington University in St. Louis.  Dr Broderick’s academic interests include thoracic surgery clinical outcomes and perioperative applications of systemic therapy for NSCLC.  His clinical interests include thoracic surgical oncology as well as the breadth of benign conditions of the chest and foregut.

Linda Martin

Abstract Presenter

Linda Martin is a Tenured Professor of Surgery at University of Virginia. She is Chief of Thoracic Surgery, leads the Thoracic Oncology Tumor Board, and co-leads Enhanced Recovery Program for Thoracic Surgery. She is a member of the International ERAS Society Thoracic guidelines team. Since 2019, she has been recognized for achieving 99^th% Press-Ganey patient satisfaction scores for 6 consecutive years. She was awarded the Dean's Clinical Excellence Award in 2022. She served as the Clerkship Director for the Dept. of Surgery 2017-21, and in 2019 became the Associate Program Director for Cardiothoracic Residency at UVA. She has been nominated by her physician peers as a Top Doctor in Baltimore (2015), Top Doctor in Virginia (2018, 2023), and Best Practice Award in 2015 for providing excellent, timely access to high quality care with the highest level of patient and referring doctor satisfaction. At UVA, her team has achieved 3 star STS rating for lobectomy quality multiple times, and recently for esophagectomy.

Her work with IASLC includes co-chairing the 2024 World Lung conference, and appointment to the 10th edition staging committee for lung cancer. She is Vice-Chair for Respiratory Cancers for the Alliance, and also leads the Thoracic Surgery group. She serves as the STS representative to the Commission on Cancer. She is a lead investigator of multiple Alliance trials, and a global PI of an industry stage 3 lung cancer trial. She was appointed to the Thoracic Malignancy Steering Committee for the NCI in 2024, a clearing house for NCI sponsored clinical trial concepts. She is Vice-Chair of the General Thoracic Surgical Club and will ascend as the Chair in 2026. She serves on several Workforce Groups in the STS and committees for AATS. She is an exam writer for SESAP and SESAT. She became a member of AATS in 2019. She is an editor for the Operative Standards for Cancer Surgery, and an editor for Clinical Lung Cancer.

 

Specialties: Thoracic