Real-World Treatment Outcomes and Safety of Afatinib in Advanced Squamous Cell Lung Cancer Progressed after Platinum-Based Doublet Chemotherapy and Immunotherapy (SPACE Study)

Simple Summary Although the LUX-Lung 8 trial has demonstrated the clinical benefit of afatinib as a second-line treatment for squamous cell carcinoma of the lung (LSCC), data on its use as a later-line treatment and sequential treatment following immunotherapy remain underexplored. This study on the real-world evidence of afatinib in LSCC patients who progressed both after chemotherapy and immunotherapy showed encouraging clinical outcomes with 2.1 months of time to treatment failure (TTF) and a 59.5% disease control rate in those patients without new safety signals. In addition, the erythroblastic oncogene B 2 (ERBB2) mutation was significantly associated with a longer TTF than the wild type. To the best of our knowledge, this is the first real-world study to demonstrate treatment outcomes, safety, and molecular biomarkers of afatinib in LSCC regardless of prior treatment lines. The present data may provide valuable insights for better management of patients with LSCC in routine clinical practice.Abstract This study aimed to evaluate treatment outcomes and safety of afatinib in patients with squamous cell carcinoma of the lung (LSCC) who progressed after chemotherapy and immunotherapy. We recruited patients both retrospectively and prospectively and collected the outcomes and safety data. Additionally, we performed next-generation sequencing using tumor tissue and/or plasma to explore potential molecular biomarkers. Altogether, 42 patients were included in the final analysis. The median number of prior treatments was three (range 1-8), and the median TTF was 2.1 months. Objective response rate and disease control rate were 16.2% and 59.5%, respectively, and median duration of response was 4.0 months among response evaluable patients (n = 37). Treatment-related adverse events (TRAEs, including diarrhea, stomatitis, and paronychia) occurred in 22 (52.3%) patients; however, most were grade 2 or lower, and only 5 cases were grade 3. TRAEs led to dose modification in 17 (40.5%) and discontinuation in 4 (9.5%) patients. The TTF in patients with ERBB2 mutations was significantly longer than that in patients without (6.8 vs. 2.1 months, p = 0.045). Our results highlight that afatinib is a reasonable treatment option in terms of effectiveness and safety, and ERBB2 mutation can be used as a predictive biomarker in clinical settings.