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.
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).
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.
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.
Clinical trial identification
Legal entity responsible for the study
Medical Oncology Department, Hospital de la Santa Creu i Sant Pau.
Has not received any funding.
All authors have declared no conflicts of interest.