Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancer.

Introduction: For most locally advanced non-small cell lung cancer (LA-NSCLC) patients who complete definitive chemoradiotherapy (CRT) and do not experience disease progression, one year of adjuvant durvalumab is recommended. Here, we explore causes and consequences of early durvalumab discontinuation. Materials and Methods: We reviewed patients treated for LA-NSCLC with definitive CRT who began adjuvant durvalumab between 2017 and 2021. Duration of durvalumab receipt and causes for early discontinuation were tabulated. Logistic regression models were utilized to evaluate predictors of early durvalumab discontinuation. Landmark analyses were performed to explore associations between early durvalumab discontinuation and clinical outcomes (progression-free survival (PFS), overall survival (OS)). Results: Fifty-nine patients were included. Forty-one patients (69%) discontinued durvalumab early, most commonly for disease progression (n = 14) or lung toxicity (n = 10). Multivariable analysis revealed mean heart radiotherapy dose (MHD) was associated with risk of durvalumab discontinuation from progression (HR = 2.34 per 10 Gy, p = 0.052), and there was a trend suggesting an association between MHD and risk of durvalumab discontinuation from lung toxicity (HR = 2.16 per 10 Gy, p = 0.126). Median PFS duration following durvalumab initiation was 14 months, and median OS duration was 32 months. Landmark analyses that excluded patients with progression or death within one year of durvalumab initiation demonstrated improved outcomes for patients who completed one year of durvalumab (2-year PFS 100% v. 40%, p < 0.001; 2-year OS 100% v. 67%, p = 0.862). Improved outcomes were observed for patients who received MHD below the cohort median (9.3 Gy) compared to patients with higher MHD (median PFS 32 months v. 8 months, p < 0.001; 2-year OS 69% v. 44%, p = 0.088). Conclusion: For LA-NSCLC patients treated with CRT followed by immunotherapy, extent of cardiac irradiation may be a risk factor for immunotherapy discontinuation, disease recurrence, and death.