Impact of immune-related adverse events (irAEs) on PD-1/L1 inhibitors efficacy in advanced esophageal cancer.

Abstract

4061 Background: The recent development of Immune checkpoint inhibitors (ICIs) has improved treatment outcomes for patients with esophageal cancer, although it may initiate autoimmune-related disorders in some patients. Across disease sites, patients who experience irAEs while on therapy with anti-PD-1 and anti-PD-L1 antibodies have been documented to experience improved outcomes as measured by overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Methods: We reviewed the medical records and the following characteristics of patients were collected: age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), stage, histology, history of surgery, metastatic sites, therapy line, presence of target lesion according to the response evaluation criteria in solid tumors (RECIST) version 1.1, LDH level before initiating ICIs treatment. We divided the patients treated with ICIs into two groups based on occurrence of irAEs. We compared the efficacy between the irAE - and irAE + groups. Results: There were total 295 patients. Of all the patients, 143 patients (50.2%) suffered from irAEs. The median patient age was 60 years (range, 36–84). Baseline characteristics including gender, ECOG PS, tumor location, history of surgery, histology, number of organs with metastases, site of metastases, therapy line, history of drinking, history of smoking between patients with or without irAE were not significantly different. The most frequent irAEs were Anemia(71/295, 24.07%), Pneumonitis (55/295, 18.64%), Cardiovascular toxicities (35/295, 11.86%). There were no grade 5 adverse events related to immunotherapy. Objective response was observed in 92 patients (31.19%), 54 of the 143 patients with irAEs had objective response (37.76%) in contrast with 38 of the 152 cases without irAEs (25.00%). Median PFS in patients with irAEs was 10.27 months and 6.2 months in those without irAEs (p<0.001). Median OS in patients with irAEs was 15.4 months and 9.2 months in those without irAEs(p<0.001).Multivariate analyses identified an ECOG PS ≥2, cycles ≤8, and without irAEs as independent poor prognostic factors (p=0.003, p <0.001 and p=0.011). Multivariate analysis demonstrated that ECOG PS ≥2, Therapy line≥22nd,without radiation and absence of irAEs were associated with a poor overall survival(p=0.022, p=0.006, p. <0.001 and p=0.002). Multivariable analysis also revealed that Cycles>8, Radiation and Antiangiogenic therapy were positively associated with occurrence of irAEs(p<0.001, p=0.002, p=0.025). Conclusions: In advanced esophageal cancer treated with PD-1/L1 inhibitors., patients with irAEs showed a markedly improved efficacy over patients without irAEs.