E. S. Lebow1, K. J. Fitzgerald2, N. Shaverdian3, R. Kotecha4, D. R. Gomez3, A. J. Wu3, D. Gelblum3, A. F. Shepherd3, C. B. Simone II5, Z. Zhang6, N. Toumbacaris6, E. D. Yorke7, J. Eng8, K. Ng8, A. Iqbal8, M. G. Kris9, and A. Rimner3,10; 1University of Pennsylvania, Philadelphia, PA, 2Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, NY, 3Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 4Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 5New York Proton Center, New York, NY, 6Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 7Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, 8Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 9Memorial Sloan Kettering Cancer Center, New York, NY, 10Department of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK), partner site DKTK-Freiburg, Freiburg, Germany
Purpose/Objective(s): Nearly half of patients with inoperable, locally advanced non-small cell lung cancer (LA-NSCLC) are not candidates for concurrent chemoradiation therapy (cCRT) followed by consolidative durvalumab. This investigator-initiated multi-institutional trial evaluated definitive radiation therapy (RT) with concurrent and consolidative durvalumab without chemotherapy among patients who were not candidates for cCRT. Materials/Methods: This single-arm, open label phase II study included patients with inoperable LA-NSCLC unselected by PD-L1 expression who were treated with conventionally fractionated definitive RT (60 Gy in 30 fractions). Concurrent durvalumab (1500 mg every 4 weeks) was initiated within 7 days of RT start and continued for up to 13 cycles, in the absence of disease progression or unacceptable toxicity. The primary objective of the study was an improvement in 2-year progression-free survival (PFS) rate compared to historical results of RT alone (20% 2-year PFS) using a one-sided test based on the Kaplan-Meier method. Cox models were utilized for univariable analyses of PFS and overall survival (OS). PD-L1 status was categorized as positive or negative for the Cox analysis.
Results: A total of 53 patients with a median age of 80.6 years were enrolled. No early stopping safety rules were met. Eight patients (15%) had a KPS of 50 - 60, 41 patients (77%) had KPS 70 – 80, and 4 patients (8%) had KPS 90. The median number of durvalumab cycles was 8 (range: 1-13). At the time of analysis, the median follow-up was 19.4 months (95% CI 13.5, 28.4). For the primary analysis, the lower bound of the 1-sided 95% CI of 2-year PFS rate is 28% which is above the pre-specified threshold of 20%. For secondary analyses, the median PFS was 14 months (95% CI 10 months – not reached). The 6-, 12-, and 24-month PFS rates were 80% (95% CI 69% – 92%), 56% (95% CI 43%, 73%), and 39% (95% CI 26% - 58%), respectively. The median OS was 25 months (95% CI 17 months – not reached). The 6-, 12-, and 24-month OS rates were 84% (95% CI 74% - 95%), 79% (95% CI 68% - 92%), and 53% (95% CI 39% - 73%), respectively. On univariable Cox analysis of PFS, KPS (HR=0.95, 95% CI 0.91-0.99, p=0.023), PD-L1 status (HR=0.45, 95% CI 0.20-0.98, p = 0.046) and number of durvalumab cycles (HR=0.78, 95% CI 0.71–0.86, p < 0.001) were significantly associated with PFS. Similarly, on univariable Cox analysis of OS, the patient KPS (HR=0.94, 95% CI 0.90-0.99, p = 0.023), PD-L1 status (HR=0.37, 95% CI 0.14–0.98, p = 0.046), and number of durvalumab cycles (HR=0.81, 95% CI 0.72–0.91, p < 0.001) were significantly associated with OS.
Conclusion: Definitive RT with concurrent and consolidative durvalumab without chemotherapy shows promising PFS and OS results in a patient population not eligible for cCRT. KPS, PD-L1 status, and number of durvalumab cycles are significantly associated with survival on univariable analysis.
