One-Year Disease Outcomes in Stage III Non-Small Cell Lung Cancers Treated with Trimodality Therapy vs Concurrent Chemoradiation and Durvalumab

Abstract

Trimodality therapy with surgical resection, chemotherapy and radiation results in improved disease control compared to concurrent chemoradiation (cCRT) alone in patients with stage III non-small cell lung cancer (NSCLC). While trials investigating PD-1 directed therapies in surgically treated NSCLCs are ongoing, durvalumab after cCRT in unresected NSCLCs has been found to improve survival and is standard practice. To further gauge the impact of durvalumab on improving outcomes in patients with unresected stage III NSCLCs, we compared disease outcomes between patients treated with trimodality therapy and cCRT + durvalumab. Patients with stage III NSCLCs with clinical N2 disease treated between 1/2010 – 5/2019 were reviewed. Trimodality patients underwent R0 resection with standard of care neo/adjuvant chemotherapy and post-operative radiation therapy. Patients treated with cCRT + durvalumab received ≥1 dose of durvalumab. Estimates for 12-month overall survival (OS), progression-free survival (PFS) and incidence of distant metastases (DM) were calculated from the date of surgery or start of cCRT and compared using the Log-Rank and Gray’s test. Baseline characteristics were compared using the Fisher’s exact and Wilcoxon test. In total, 125 patients were evaluated of which 88 received trimodality therapy (median follow-up: 31 months) and 37 received cCRT + durvalumab (median follow-up: 16 months). The median age was 66 and 67 years for trimodality and cCRT + durvalumab patients, respectively (p = 0.1). Compared to patients treated with cCRT + durvalumab, more patients treated with trimodality therapy were female (58% vs 38%, p = 0.05), ECOG 0 (78% vs 47%, p<0.01), never smokers (15% vs 0%, p = 0.01), and had T1-T2 disease (73% vs 43%, p<0.01). Among trimodality patients, 7% (n = 6) underwent a pneumonectomy, 75% (n = 66) received neoadjuvant chemotherapy, 64% (n = 56) were treated with a cisplatin-based regimen, and all (n = 88) had pathological N2 disease. Among cCRT + durvalumab patients, patients started durvalumab a median of 1.5 months from completion of cCRT and were treated with a median of 5 months of durvalumab. Estimates for 12-month OS, PFS and incidence of DM for trimodality therapy vs cCRT + durvalumab patients are: 92% (95% CI: 86 -98%) vs 89% (78 - 99%) (p = 0.84), 67% (57 - 77%) vs 76% (62 - 89%) (p = 0.18), and 31% (21 - 41%) vs 17% (4 - 29%) (p = 0.06), respectively. While surgical management is standard of care for appropriately selected patients with stage III NSCLCs, our data suggest that patients with unresected disease treated with cCRT + durvalumab can achieve outcomes comparable to those treated with trimodality therapy. These data further support the use of durvalumab after cCRT in unresected NSCLC, and trials investigating PD-1 directed therapies in patients with surgically treated NSCLCs.