Does Adjuvant Durvalumab Improve Local Control Following Chemoradiotherapy for Non-Small Cell Lung Cancer?

Abstract

<h3>Purpose/Objective(s)</h3> Analyses of the PACIFIC trial have demonstrated that treatment with durvalumab after chemoradiotherapy (CRT) for stage III non-small cell lung cancer (NSCLC) improves overall survival, progression-free survival (PFS), and intrathoracic disease control. We reviewed outcomes for patients treated with and without adjuvant durvalumab to assess if durvalumab improves local control of the tumors and lymph nodes treated with radiotherapy. <h3>Materials/Methods</h3> We reviewed locally advanced NSCLC patients who underwent PET staging and received definitive concurrent CRT at our institution between 2007 and 2021. Patients with disease progression or death within six weeks after radiotherapy completion were excluded. Based on previous patterns-of-failure analyses, tumors and lymph nodes were categorized as high- or low-risk for local failure using a metabolic tumor volume cutoff of 25 cc. Kaplan-Meier curves and Cox proportional hazards models were used to test durvalumab receipt as a predictor of PFS. Competing risks analyses were performed to test durvalumab receipt as a predictor of local progression of treated tumors and lymph nodes. Progression at other sites and death without progression were treated as competing risks. <h3>Results</h3> 197 patients with 567 hypermetabolic lesions treated with radiotherapy (192 pulmonary tumors, 375 lymph nodes) met inclusion criteria. Among 84 patients with known PD-L1 tumor proportion score (TPS), TPS was <1% for 28 patients (33%), 1-49% for 34 patients (40%), and ≥50% for 22 patients (26%). Sixty-three patients (32%) received adjuvant durvalumab. The median follow-up duration was 57 months for patients who did not receive durvalumab and 27 months for patients who received durvalumab. The median PFS duration for patients who received durvalumab was 16.2 months, compared to 10.5 months for patients who did not receive durvalumab (HR=0.70, 95% CI 0.48 to 1.02, p=0.064). However, we found no significant association between durvalumab receipt and cumulative incidence rate (CIR) of local failure for high- or low-risk lesions (See Table). In a multivariable model adjusted for lesion size and durvalumab receipt, high PD-L1 TPS was associated with reduced risk of local failure (p=0.033). <h3>Conclusion</h3> For locally advanced NSCLC patients treated with definitive CRT, we did not find that adjuvant durvalumab improves local disease control. This suggests that durvalumab improves outcomes by preventing ‘out-of-field' progression. Strategies to improve local control of large tumors and lymph nodes should still be explored.