Durvalumab With Radiation Therapy in Patients With Inoperable Locally Advanced Non–Small Cell Lung Cancer Ineligible for Concurrent Chemoradiotherapy (DART)
Abstract
PURPOSE Concurrent platinum-based chemotherapy and radiation therapy (cCRT) followed by consolidative durvalumab is the standard of care (SoC) for fit patients with inoperable, locally advanced non–small cell lung cancer (LA-NSCLC). However, no SoC exists for patients who are cCRT-ineligible because of age, comorbidities, or frailty. Here, we investigated the efficacy and adverse events (AEs) of concurrent and consolidative durvalumab with definitive radiation therapy (RT) without chemotherapy. METHODS In this multicenter, single-arm, prospective phase II study, patients received conventionally fractionated RT plus concurrent and consolidative durvalumab (1,500 mg fixed dose once every 4 weeks) for up to 12 months. The primary end point was 2-year progression-free survival (PFS) of 36% compared with historical results of 20% with sequential CRT (86% power). Additional end points included overall survival (OS) and cancer-specific survival (CSS). RESULTS Fifty-eight patients (median age 82 years [IQR, 76-86]; 16 [28%] PD-L1–negative; eight [14%] Eastern Cooperative Oncology Group [ECOG] score 2; 46 [79%] ECOG score 1; four [7%] ECOG score 0) were treated per protocol. The study met its primary end point with a 2-year PFS of 39% (one-sided CI, 29 to 100) and a 2-year OS of 54%. Better performance status and PD-L1 positivity were associated with improved PFS; better ECOG was associated with improved OS; PD-L1 positivity was associated with better CSS. Grade 3/4 treatment-related AEs occurred in 12 (21%) patients. Grade 5 AEs occurred in four (7%) patients (radiation pneumonitis (n = 2) and cardiac arrest (n = 2)). Durvalumab was discontinued early because of AEs in 18 (31%) patients. CONCLUSION Thoracic RT with concurrent and consolidative durvalumab is a promising treatment option for cCRT-ineligible patients with LA-NSCLC, demonstrating better PFS with a favorable safety profile compared with historical controls.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (26)
Andreas Rimner
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Emily S. Lebow
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Kelly J. Fitzgerald
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Leah Kratochvil
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Nicolas Toumbacaris
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
Daphna Y. Gelblum
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Rupesh Kotecha
Daniel R. Gomez
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Abraham J. Wu
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Annemarie F. Shepherd
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Ellen D. Yorke
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY
Juliana Eng
Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY
Kenneth Ng
Gregory J. Riely
Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY
Afsheen Iqbal
Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY
Charles M. Rudin
David R. Jones
MPA-Center for Integrated Nanotechnologies, Los Alamos National Laboratory 2 , Los Alamos, New Mexico 87545,
James M. Isbell
Gaetano Rocco
Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
Valerie W. Rusch
Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
Michelle S. Ginsberg
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
Zhigang Zhang
Charles B. Simone
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Mark G. Kris
Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY
Narek Shaverdian
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Jamie E. Chaft
Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY