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

• Published in: Cancers Vol. 14; no. 13; p. 3226
• Main Authors: Wass, Romana, Hochmair, Maximilian, Kaiser, Bernhard, Grambozov, Brane, Feurstein, Petra, Weiß, Gertraud, Moosbrugger, Raphaela, Sedlmayer, Felix, Lamprecht, Bernd, Studnicka, Michael, Zehentmayr, Franz
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-06-2022; MDPI
• Subjects: Chemoradiotherapy; Chemotherapy; Clinical trials; Disease control; Drug dosages; Gemcitabine; Histology; Immunotherapy; Medical imaging; Non-small cell lung carcinoma; Patients; PD-L1 protein; Pneumonia; Pneumonitis; Positron emission tomography; Radiation therapy; Small cell lung carcinoma; Taxotere; Thorax; Toxicity; Vinorelbine; toxicity; chemoradiotherapy; durvalumab; pneumonitis; high dose radiation
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14133226

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.