Prevention of pemetrexed-induced rash with low-dose dexamethasone in patients with NSCLC receiving immunotherapy: A prospective, single-arm clinical trial.

Abstract

e20596 Background: Pemetrexed is highly active in non-small cell lung cancer (NSCLC). Rashes associated with pemetrexed are more commonly than other chemotherapies. It is recommended that patients receive pemetrexed are required dexamethasone as a pretreatment. However, the immunosuppressive effects of dexamethasone especially high doses of glucocorticoids may reduce the efficacy of immune checkpoint inhibitors (ICIs). This study aims to prospectively evaluate the efficacy of low-dose dexamethasone in pretreatment of pemetrexed-induced rash, particularly in NSCLC patients receiving immunotherapy. Methods: This is a prospective, single-arm clinical trial that enrolled NSCLC patients scheduled to receive chemotherapy including pemetrexed, with/without immunotherapy. Patients received low-dose dexamethasone: 8mg, 4mg, 2 mg of dexamethasone for 3 days recpectively from the day preceding pemetrexed (the recommended administration is 8 mg/day of dexamethasone for 3 days) . Rash severity is described according to CTCAE v5.0 (Common toxicity criteria for adverse events version 5.0). The primary endpoint was the 3-week incidence of rash after pemetrexed. Results: A total of forty-seven stage IIB-IVB patients were enrolled between February 2022 and December 2023, including eighteen patients were combined with immunotherapy. They all received the low-dose dexamethasone regimen prior to a total of 149 cycles of chemotherapy. The incidence of skin rash after 3 weeks was of 7 episodes in 149 cycles (4.70%), 7 patients (12.77%) presented rash. In the eighteen patients receiving immunotherapy, rash within 3 weeks after pemetrexed administration occurred in 4 episodes in 72 cycles (5.56%), 4 patients ( 22.22%) presented rash. And one patient presented two episodes of cutaneous toxicity. Most skin rash episodes were of grade 1 (approximately 85%), while the rest were grade 2 (approximately 15%). No grade 3 or 4 skin rash was reported in the entire study population. Most cutaneous toxicities occurred during the first or second cycle. The incidence of rash in this study was significantly lower than the rate of 67.5-93% reported in patients treated without corticosteroids and did not increase compared with the rate of 14-56% reported in patients treated with corticosteroids. Conclusions: Administration of low-dose dexamethasone (8mg, 4mg, 2 mg of dexamethasone for 3 days from the day preceding pemetrexed) significantly reduces the incidence of rash after pemetrexed. The regimen may provide a standard preventive strategy for pemetrexed-induced rash, especially in NSCLC patients combined with immunotherapy(This study is registered with the Chinese Clinical Trial Registry (ChiCTR2400079622). Clinical trial information: ChiCTR2400079622.