Incidence of Pneumonitis in Consolidative Durvalumab Era and its Correlation with Lung Dose-Volumes Histograms in Stage III Nonresectable Non-Small Cell Lung Cancer (NCSLC)

Abstract

<h3>Purpose/Objective(s)</h3> Durvalumab has been the standard of care following chemoradiation in stage III nonresectable NSCLC since the PACIFIC trial in 2017. Even though the incidence of any grade pneumonitis in the PACIFIC trial was only 9.1%, other studies have suggested that real world incidence of pneumonitis rate with consolidative Durvalumab is as high as 49%. We undertook this retrospective study to compare the incidence of pneumonitis in the pre and post Durvalumab era and its relationship with radiation dose parameters. <h3>Materials/Methods</h3> An IRB approved retrospective chart review study was conducted for patients with stage III nonresectable NSCLC who were diagnosed between January 1, 2012 and December 31, 2019 at our institution and received chemoradiation (CRT) alone or with consolidative Durvalumab. Patients who did not receive Durvalumab after it became standard of care were included in the CRT alone group. Patients with incomplete records were excluded. Radiotherapy data was collected from delivered radiation plans. Fisher's exact test was used to compare the difference in the rate of pneumonitis between CRT alone versus CRT with Durvalumab groups. Univariable logistic regression was performed to identify risk factors for pneumonitis and variables with p < 0.1 were included in a final multivariate logistic regression. Analysis was performed using R (version 4.1.2). <h3>Results</h3> 110 out of 166 patients were included in the final analysis. The median age of diagnosis was 64.5 years (range 39-86) with 56 being female (51%) gender. Fifty-eight patients were white (53%), while 41 African American (37%), and 11 unknown. Adenocarcinoma (50%, n=55) was most common histology followed by squamous cell carcinoma (44%, n=48), and others (6%, n=7). 94 (85%) patients received CRT alone and 16 (15%) received CRT with consolidative Durvalumab. 72 (65%) had right and 36 (33%) had left primary, and 2 mixed. There was a significant difference in the rate of symptomatic pneumonitis between CRT alone (21%) versus CRT with consolidative Durvalumab (56%) (p = 0.009). The mean lung V20 was 26% (1% - 50%), V10 was 36% (8% - 70%), and V5 47% (10% - 87%) with an average mean lung dose of 14 Gy. On univariable analysis, only V20 and Durvalumab were significant in predicting pneumonitis with p<0.05, lung mean dose with borderline significance (p<0.07) while V10, V5, age, sex, race and laterality were not. A multivariate model including Durvalumab, V20, and lung mean dose showed only Durvalumab to be significant (p = 0.01). <h3>Conclusion</h3> Our study showed compared to CRT alone, consolidative Durvalumab was associated with a significant increase in the rate of symptomatic pneumonitis. Further research is needed to understand the interaction between the radiation parameters of lung and Durvalumab.