Association of immune-related adverse (irAEs) with immunecheckpoint inhibitors (ICIs) efficacy in solid tumors

Background: ICIs can induce irAEs that may compromise treatment continuation. We report the incidence of irAEs in patients (pts) with solid tumors receiving ICIs and its correlation with efficacy. Methods: We retrospectively analyzed 178 pts with solid tumors receiving ICIs in our institution from 3/2014 to 1/2018. IrAEs were graded following CTCAE v4.0. Kaplan Meier and log-rank tests were used to evaluate progression-free and overall survival (PFS, OS). Results: Median age was 64.1 [33-88] years, 72% male. Most common tumors were lung (63.5%), bladder (14.6%) and melanoma (11.8%). 96% had advanced disease. Most frequent ICIs were nivolumab (38.2%), pembrolizumab (28.7%) and atezolizumab (17.4%), used as monotherapy (74.7%) or in combination with ICIs (3.4%), chemotherapy (17.4%) or targeted therapies (4.5%). Median duration of treatment was 2.1 [0.5-26.5] months. 95 (53.4%) pts developed 158 irAEs, mean 1.2 [0-4] irAEs/pts. Most frequent irAEs were rash (24.7%), diarrhea (17.7%), pruritus (17.7%), thyroid dysfunction (13.3%), arthritis (6.9%), hepatitis (3.8%), pneumonitis (3.2%). 12 (6.7%) pts presented grade (G) 3-4 irAEs: 4 diarrhea, 2 liver dysfunction, 1 pneumonitis, 1 hypopituitarism, 1 mucositis, 1 arthritis, 1 nephritis and 1 haemolytic anemia. 2 treatment-related deaths due to pneumonitis were reported. 15 (8.4%) pts discontinued treatment due to irAEs. At the time of data analysis, 89.2% of irAEs had improved. With a median follow-up of 7.0 [0.5-46.3] months, median OS was superior in pts with advanced disease experiencing irAEs: 37.3 [95%CI, 19.2-51.4] vs 7.8 [95%CI, 4.9-10.8] months (p < 0.0001). Similarly, PFS was higher: 7.9 [95%CI, 4.4-11.4] vs 2.6 [95%CI, 2.0-3.2] months (p < 0.0001). 82 (46%) pts required systemic corticosteroids during therapy, 31.7% for irAEs management. OS was longer in pts who did not receive steroids: 35.3 [95%CI, 13.5-57.1] vs 10.2 [95%CI, 4.7-15.7] months (p 0.007). No association was found between efficacy and use of antibiotics in the 3 months before first ICIs injection or during treatment. Conclusions: Development of irAEs in pts with advanced solid tumors treated with ICIs was associated with efficacy. A negative correlation between use of systemic corticosteroids and outcomes was found. Legal entity responsible for the study: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.