The profile and clinical predicting effect of non-rash dermatologic toxicity related to targeted therapy in stage-IV non-small cell lung cancer patients

Dermatologic toxicities associated with targeted therapies may impact drug intolerance and predict drug response, among which rash is most frequently reported and well delineated. However, the profile and effect of non-rash dermatologic toxicity are not fully understood. We identified stage-IV non-small cell lung cancer patients diagnosed at Mayo Clinic in 2006-2019 and systematically analyzed demographics, targeted agents, toxicity, response, and survival outcomes of patients who received targeted therapy. Five toxicity subgroups-none, only non-rash dermatologic, concurrent non-rash and rash (concurrent) dermatologic, only rash, and others-were compared; multivariable survival analyses employed Cox Proportional Hazard models. This study included 533 patients who had taken targeted therapies: 36 (6.8%) had no toxicity, 26 (4.9%) only non-rash dermatologic, 193 (36.2%) only rash, 134 (25.1%) concurrent dermatologic, 144 (27.0%) other toxicities. Non-rash dermatologic toxicities predominately included xerosis (12.8%), pruritus (8.5%), paronychia (7.0%). Rash was the most frequent (59.4%) and the earliest occurring (21 median onset days [MOD]) dermatologic toxicity; paronychia was the latest (69 MOD) occurring. In 329 epidermal growth factor receptor inhibitors-treated patients with dermatologic toxicity, mild toxicity occurred the most frequently in patients with only non-rash (81.8%), then those with only rash (64.8%), and the least in the concurrent (50.4%, P=0.013). Patients with concurrent dermatologic toxicities had a significantly higher response rate (67.9%) than those with only non-rash (53.8%) or only rash (41.1%, p < 0.001). Multivariable analysis demonstrated concurrent dermatologic toxicity independently predicted a lower risk of death (harzard ratio [HR] 0.48 [0.30-0.77], p < 0.001). Compared to rash, non-rash dermatologic toxicity might be a stronger predictor of better treatment response and longer survival in patients who received targeted therapy.