Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Trospective Comparison Focusing on Pulmonary Toxicity

Romana Wass; Maximilian Hochmair; Bernhard Kaiser; Brane Grambozov; Petra Feurstein; Gertraud Weiß; Raphaela Moosbrugger; Felix Sedlmayer; Bernd Lamprecht; Michael Studnicka; Franz Zehentmayr

doi:10.3390/cancers14133226

Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Trospective Comparison Focusing on Pulmonary Toxicity

Cancers (Basel). 2022 Jun 30;14(13):3226. doi: 10.3390/cancers14133226.

Authors

Affiliations

¹ Department of Pulmonology, Paracelsus Medical University, A-5020 Salzburg, Austria.
² Department of Pulmonology, Kepler University Hospital, A-4020 Linz, Austria.
³ Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Cancer Research and Pulmonary Oncology, Klinik Floridsdorf, A-1210 Vienna, Austria.
⁴ Department of Radiation Oncology, Paracelsus Medical University, A-5020 Salzburg, Austria.
⁵ Department of Radiation Oncology, Klinik Ottakring, A-1160 Vienna, Austria.
⁶ radART-Institute for Research and Development on Advanced Radiation Technologies, Paracelsus Medical University, A-5020 Salzburg, Austria.

Abstract

Introduction: The standard of care (SoC) for unresectable stage III non-small-cell lung cancer (NSCLC) is durvalumab maintenance therapy after concurrent chemoradiation in patients with PD-L1 > 1%. However, the concurrent approach is only amenable for about one-third of patients due to co-morbidities. Although sequential regimens are usually not regarded as curative, these schedules applied in a dose-escalated manner may be similarly radical as SoC. As combining high-dose radiation and durvalumab remains a question of debate this retrospective bi-center study aims to evaluate pulmonary toxicity after high-dose chemoradiotherapy beyond 70 Gy compared to SoC. Patients and Methods: Patients with NSCLC stage III received durvalumab after either sequential high-dose chemoradiation or concomitant SoC. Chemotherapy consisted of platinum combined with either pemetrexed, taxotere, vinorelbine, or gemcitabine. The primary endpoint was short-term pulmonary toxicity occurring within six months after the end of radiotherapy (RT). Results: A total of 78 patients were eligible for this analysis. 18F-FDG-PET-CT, cranial MRT, and histological/cytological verification were mandatory in the diagnostic work-up. The high-dose and SoC group included 42/78 (53.8%) and 36/78 (46.2%) patients, respectively, which were matched according to baseline clinical variables. While the interval between the end of RT and the start of durvalumab was equal in both groups (p = 0.841), more courses were administered in the high-dose cohort (p = 0.031). Pulmonary toxicity was similar in both groups (p = 0.599), whereas intrathoracic disease control was better in the high-dose group (local control p = 0.081, regional control p = 0.184). Conclusion: The data of this hypothesis-generating study suggest that sequential high-dose chemoradiation followed by durvalumab might be similar to SoC in terms of pulmonary toxicity and potentially more effective with respect to intra-thoracic disease control. Larger trials with a prospective design are warranted to validate these results.

Keywords: chemoradiotherapy; durvalumab; high dose radiation; pneumonitis; toxicity.

Grants and funding

This publication was supported by AstraZeneca. AstraZeneca had no influence on the manuscript and the authors are responsible for all content and editorial decisions.