In addition to inducing clinical responses, cancer immunetherapy may awaken autoimmune disorders. We have attempted to establish if the incidence of any irAE after Nivolumab used in advanced malignant diseases is associated with anti-PD-1 treatment efficacy.
We studied all advanced cancer patients treated with Nivolumab between January 2016 and September 2017 at our institution. IrAEs were identified according to CTCAE-4.0. Efficacy was evaluated with objective response rate (ORR, immune RECIST criteria) and progression free survival (PFS). Odds Ratio tests were performed to determine the association between irAEs and ORR.
Finally, 64 patients were included. Primary tumor diagnosis were: lung cancer (n = 47), squamous cell carcinoma of head and neck (n = 5), melanoma (n = 4), clear cell renal carcinoma (n = 4), Hodgkińs lymphoma (n = 2), and urothelial bladder carcinoma and gallbladder adenocarcinoma (n = 1, each one). IrAEs were observed in 27 patients (42.2%), and included hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4) as more frequent. ORR was observed in 28 patients (43.7%). Median PFS was 6 months (1-25). 21 of the 27 patients with irAEs had objective response (77.7%) vs 7 of the 37 cases without irAEs (18.9%) (OR 15.0, p < 0.000001). PFS in patients with irAEs vs non-irAEs was 7 vs 5 months (HR 2.2, p = 0.016). These results were independent of cancer type, age, sex, histology, ECOG performance status, smoking habit or prior lines of therapy.Table: 1227P
Descriptions of patients who developed irAEs
|irAE Category||TOTAL patients N. (% Total Patients)||irAEs Grade 1-2 N.||irAEs Grade 3-4|
|Hypothyroidism + Hypophysitis + Panhypopituitarism + Suprarrenal Insufficiency + Hepatits + Pneumonitis||1 (1.5%)||1 (Hypophysitis + Panhypopituitarism + Suprarrenal Insufficiency + Hepatits + Pneumonitis)||1 (Hypothyroidism)|
|Hypothyroidism + Hyperthyroidism + Ketoacidotic Diabetes||1 (1.5%)||1 (Hypothyroidism + Hyperthyroidism)||1 (Ketoacidotic Diabetes)|
|Hypothyroidism + Hyperthyroidism||1 (1.5%)||1||0|
|Hypothyroidism + Nephritis||2 (3.2%)||2||1 (Nephritis in one of the patients)|
|Nephritis + Arthritis||1 (1.5%)||1 (Arthritis)||1 (Nephritis)|
|Rash + Encephalitis||1 (1.5%)||1 (Rash)||1 (Encephalitis)|
|Total patients irAEs||27 (42.2%)||20 irAEs in grade 1-2||11 irAEs in grade 2-3|
|Patients without irAEs||37 (57.8%)||-||-|
In advanced cancer patients treated with an anti-PD-1 antibody, the incidence of irAEs after Nivolumab is associated with a dramatically improved ORR and PFS. Future studies of anti-PD-1 cancer immunotherapy will need to address this association of toxicity and efficacy in order to reveal the underlying biological mechanisms.
Clinical trial identification
Legal entity responsible for the study
Instituto de Investigación Sanitaria Princesa.
Has not received any funding.
All authors have declared no conflicts of interest.