Second-line afatinib or chemotherapy following immuno-chemotherapy for the treatment of metastatic, squamous cell carcinoma of the lung: real-world effectiveness and safety from a multi-site retrospective chart review in the USA

Abstract Objectives : The ErbB family blocker, afatinib, is approved for patients with squamous cell carcinoma (SqCC) of the lung following platinum-doublet chemotherapy but has not been explored following immuno-chemotherapy. Here, we assessed the characteristics and outcomes of patients with SqCC of the lung who received second-line afatinib or chemotherapy after first-line pembrolizumab plus chemotherapy in a ‘real-world’ setting. Methods : In this retrospective, multi-site cohort study, community oncologists identified eligible patients and extracted data from electronic health records. Primary outcome measures were patient demographics and clinical characteristics, time on treatment and incidence of severe immune-related adverse events (irAEs). Results : Two hundred patients were included: 99 received second-line afatinib and 101 received second-line chemotherapy. Median age was 68 and 66 years, respectively; 35% and 3% of patients had mixed histology tumors, and 39% and 5% of tumors were epidermal growth factor receptor (EGFR) mutation-positive (EGFRm+). Median time on treatment was 7.3 months with afatinib (mixed histology/SqCC tumors: 8.1/5.8 months; EGFRm+/EGFRm- tumors: 7.4/5.9 months) and 4.2 months with chemotherapy. Grade 3/4 irAEs were observed in six patients in the afatinib cohort (all had a prior grade 3/4 irAE during first-line therapy) and no patients in the chemotherapy cohort. The most common adverse drug reactions with afatinib were diarrhea (26%), rash (6%), stomatitis, fatigue and nausea (5% each). Conclusions : Encouraging time on treatment, and absence of newly-diagnosed irAEs, indicate that afatinib is a treatment option following immuno-chemotherapy in patients with SqCC of the lung, and is currently the only approved oral agent in this setting. Micro Abstract In this retrospective study, we identified 200 patients with SqCC of the lung who received first-line pembrolizumab plus chemotherapy, followed by afatinib (n=99) or further chemotherapy (n=101). Median time on treatment with afatinib (7.3 months) was encouraging with an absence of newly-diagnosed immune-related adverse events, indicating that afatinib is a treatment option in this setting, following progression on immuno-chemotherapy.