2429 - Durvalumab Concurrent and Following Thoracic Radiotherapy vs. Concurrent Chemoradiotherapy and Consolidation Durvalumab in Locally Advanced Non-Small Cell Lung Cancer: A Propensity Matched Analysis of a Prospective Trial
Presenter(s)
N. P. Mankuzhy1, L. A. Boe2, A. Rimner3, E. S. Lebow4, D. Gelblum1, A. J. Wu1, J. Y. Shin1, A. F. Shepherd5, P. Iyengar1, C. B. Simone II1,6, J. Eng7, K. Ng7, A. Iqbal7, A. J. Schoenfeld7, M. Offin7, M. G. Kris7, D. R. Gomez1, J. Chaft7, and N. Shaverdian1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 3Department of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK), partner site DKTK-Freiburg, Freiburg, Germany, 4Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 5Division of Radiation Oncology, University of Washington School of Medicine, Seattle, WA, 6New York Proton Center, New York, NY, 7Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): Durvalumab concurrent and following thoracic radiation (DART) is an investigational approach for unresected locally advanced non-small cell lung cancer (LA-NSCLC). Prior studies have raised concerns about the toxicity and efficacy of concurrent durvalumab with thoracic radiation (RT) compared to concurrent chemoradiation (cCRT) and consolidation durvalumab (PACIFIC). To compare outcomes between regimens, we conducted a propensity matched analysis of patients (pts) treated with DART on a prospective study compared to PACIFIC as standard of care.
Materials/Methods: The DART cohort (n=38) were enrolled on a single arm, phase II, non-randomized trial (NCT03999710) for pts not eligible for or declining chemotherapy. The PACIFIC cohort (n=230) were consecutively treated pts from our institutional database. All pts received at least one cycle of adjuvant durvalumab. Propensity matching was completed on age, stage, and PDL1 status and aimed to include the entire DART cohort while minimizing standard mean difference (SMD). Outcomes included overall survival (OS), progression-free survival (PFS) with the Kaplan-Meier method, and cumulative incidence of locoregional failure (LF), distant failure (DF), and any progressive disease (PD) with death as a competing risk. Univariable (UVA) Cox proportional hazards were completed, and toxicity rates were compared with the Chi-squared test.
Results: After matching, the cohort was 76 pts with 38 in each arm. SMD was 0.24 for age (median 80 [range 61, 92] in DART vs 79 [61, 87] in PACIFIC), 0.11 for PDL1+ (50% in DART vs 45% in PACIFIC), 0.16 for PDL1- (37% in DART vs 45% in PACIFIC), and less than 0.10 for remaining components. More pts treated with DART had ECOG performance status (PS) 2 compared to PACIFIC (32% vs 0%, p=0.04). Table 1 shows outcomes. The 2-year incidence of any progressive disease was 32% (DART, 95% CI: 18%, 48%) and 40% (PACIFIC, 95% CI: 24%, 55%) (p=0.60). There was no difference in LF (p = 0.70) or DF (p = 0.70). For OS, treatment arm (p = 0.03) and squamous histology (p = 0.05) were significant on UVA. For PFS, treatment arm was not significant on UVA (p = 0.30) but squamous histology was (p = 0.03). Rates of pneumonitis and durvalumab discontinuation were similar between arms.
Conclusion: Matched patients with LA-NSCLC treated with DART had similar disease control when compared to PACIFIC. The PACIFIC group had superior OS, likely influenced by better ECOG PS. Furthermore, in this older population, DART did not result in higher rates of grade 2+ pneumonitis or durvalumab discontinuation. These findings further support the investigation of DART for this patient population.
Abstract 2429 - Table 1| DART | PACIFIC | p-value | |
| Median OS (months, 95% CI) | 25 (17, -) | 50 (33, -) | 0.03 |
| Median PFS (months, 95% CI) | 15 (9, -) | 30 (17, -) | 0.27 |
| Durvalumab discontinued | 53% | 55% | >0.90 |
| Grade 2+ pneumonitis | 29% | 34% | 0.80 |
| Grade 3+ pneumonitis | 13% | 13% | >0.90 |