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 discontinuati...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Clinical and Translational Radiation Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240563082300068X |
| _version_ | 1827915215672442880 |
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| author | Michael Pennock Balazs Halmos William Bodner Haiying Cheng Rasim Gucalp Nitin Ohri |
| author_facet | Michael Pennock Balazs Halmos William Bodner Haiying Cheng Rasim Gucalp Nitin Ohri |
| author_sort | Michael Pennock |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T02:56:20Z |
| format | Article |
| id | doaj.art-3de1bf076fc042069d7aec4e564ef8fe |
| institution | Directory Open Access Journal |
| issn | 2405-6308 |
| language | English |
| last_indexed | 2024-03-13T02:56:20Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical and Translational Radiation Oncology |
| spelling | doaj.art-3de1bf076fc042069d7aec4e564ef8fe2023-06-28T04:29:52ZengElsevierClinical and Translational Radiation Oncology2405-63082023-07-0141100643Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancerMichael Pennock0Balazs Halmos1William Bodner2Haiying Cheng3Rasim Gucalp4Nitin Ohri5Albert Einstein College of Medicine and Montefiore Medical Center, Department of Radiation Oncology, 1625 Poplar Street, Suite 101, Bronx, NY 10461, United States; Corresponding author.Albert Einstein College of Medicine and Montefiore Medical Center, Department of Oncology, 1695 Eastchester Road, Bronx, NY 10461-2374, United StatesAlbert Einstein College of Medicine and Montefiore Medical Center, Department of Radiation Oncology, 1625 Poplar Street, Suite 101, Bronx, NY 10461, United StatesAlbert Einstein College of Medicine and Montefiore Medical Center, Department of Oncology, 1695 Eastchester Road, Bronx, NY 10461-2374, United StatesAlbert Einstein College of Medicine and Montefiore Medical Center, Department of Oncology, 1695 Eastchester Road, Bronx, NY 10461-2374, United StatesAlbert Einstein College of Medicine and Montefiore Medical Center, Department of Radiation Oncology, 1625 Poplar Street, Suite 101, Bronx, NY 10461, United StatesIntroduction: 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.http://www.sciencedirect.com/science/article/pii/S240563082300068XLung cancerImmunotherapyRadiotherapyDurvalumabToxicityPrognosis |
| spellingShingle | Michael Pennock Balazs Halmos William Bodner Haiying Cheng Rasim Gucalp Nitin Ohri Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancer Clinical and Translational Radiation Oncology Lung cancer Immunotherapy Radiotherapy Durvalumab Toxicity Prognosis |
| title | Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancer |
| title_full | Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancer |
| title_fullStr | Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancer |
| title_full_unstemmed | Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancer |
| title_short | Exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non-small cell lung cancer |
| title_sort | exploring causes and consequences of early discontinuation of durvalumab after chemoradiotherapy for non small cell lung cancer |
| topic | Lung cancer Immunotherapy Radiotherapy Durvalumab Toxicity Prognosis |
| url | http://www.sciencedirect.com/science/article/pii/S240563082300068X |
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