ICIs are a standard treatment in advanced NSCLC. However, ICIs can induce irAEs that may interrupt treatment. Here we report the incidence of irAEs and its correlation with efficacy.
We retrospectively analyzed 101 patients (pts) with advanced NSCLC receiving ICIs in our institution from March 2014 to January 2018. IrAEs were graded following CTCAE v4.0. Kaplan Meier and log-rank tests were used to evaluate progression-free (PFS) and overall survival (OS). Analyses were performed using SPSS v24 package.
Median age was 66.4 [37-85] years, 74.3% were male. 33 (32.7%) pts presented squamous and 68 (67.3%) non-squamous histology. Most frequent ICIs were nivolumab (50%), pembrolizumab (31%) and atezolizumab (16%), used as monotherapy (79.2%) or in combination with chemotherapy (20.8%). Median duration of treatment was 2.7 [0.6-26.2] months. 61 (60.4%) pts developed 106 irAEs, with a mean of 1.02 [0-4] irAEs/pts. Most frequent irAEs were rash (24.5%), pruritus (22.6%), diarrhea (21%), thyroid dysfuncion (10.5%), arthritis (8.5%), hepatitis (2.9%) and pneumonitis (2%). 8 (7.5%) patients experienced grade (G) 3-4 irAEs: 1 G3 pneumonitis, 4 G3 diarrhea, 1 G3 mucositis, 1 G3 nephritis and 1 G3 haemolytic anemia. There was one treatment-related death due to pneumonitis. 47 (46.5%) pts received systemic corticosteroids during immunotherapy, 29.8% for irAEs management. 11 (10.9%) pts discontinued treatment due to irAEs. At the time of data analysis, 86.8% of irAEs had improved. With a median follow-up of 8.9 [0.6-48.2] months, median OS was superior in pts experiencing irAEs: not reached (NR) vs 7.8 [95%CI, 5.2-10.5] months (p 0.001). Similarly, PFS was significantly longer: 6.2 [95%CI, 2.3-10.1] vs 2.7 [95%CI, 1.8-3.5] months (p < 0.0001). OS was higher in pts who didn't receive steroids during ICIs: NR vs 9.9 [95%CI, 6.8-13.0] months (p 0.024). No association was found between efficacy and the use of antibiotics in the 3 months before first ICIs injection or during treatment.
Development of irAEs was associated with efficacy of ICIs in pts with advanced NSCLC. A negative correlation between the 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.