The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non–small-cell lung cancer: a real-life retrospective study

Abstract

Background: Nivolumab and pembrolizumab, two PD1 inhibitors, trigger immune-related adverse events in approximately 50% of patients. Our objective was to determine whether these immunerelated adverse events are associated with patient outcomes. Patients and Methods: Retrospective cohort study, realized at the Institut Universitaire du Cancer de Toulouse, of all the patients treated with nivolumab or pembrolizumab off clinical trials. We included patients (i) diagnosed with unresectable stage III or stage IV melanoma or with recurrent stage IIIB or stage IV non-small cell lung cancer (ii) on nivolumab 3mg/kg or pembrolizumab 2mg/kg every 2 or 3 weeks respectively. Results: Of the 311 patients included (of 641 eligible subjects), 120 (38.6%) had melanoma and 191 (61.4%) had non-small cell lung cancer; 241 (77.5%) were treated with nivolumab with a median followup of 24 months (20-29). We observed 166 immune-related adverse events in 116 (37.3%) patients, categorized as "early" (onset before 12 weeks in melanoma and before 8 weeks in lung cancer) in 63 (54.3%) patients. Early and late adverse events were significantly associated with an increase in overall survival: adjusted hazard ratio 0.58 [0.41-0.84] (p = .003) and 0.28 [0.16-0.50] (p < .001) respectively. The overall response rate was significantly increased in patients with an immune-related adverse event (53.9% vs 12.9%, p < .001) Conclusions: This study validates the association between immune-related adverse events and anti-PD1 efficacy in real-life, especially if these events are delayed. Our results, along with further studies on the place of immunosuppressive drugs in the therapeutic strategy, could improve the management of these adverse events.

Association between Immune Related Adverse Events and Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

“…The correlation between irAEs and patient outcome has been recently described for different cancers [ 10 , 37 , 38 ]. The occurrence of irAEs has been found to be associated with favorable outcomes in melanoma [ 21 , 22 , 23 ], NSCLC [ 24 , 25 , 26 ] and, with only a few studies available, also in mRCC [ 27 , 28 , 29 ]. These studies corroborate the hypothesis of a direct link between antitumor response and auto-immune reactivity.…”

“…In the context of this research irAEs have been proposed as potential clinical markers to predict response to ICI. This relationship, although documented in studies regarding non-small cell lung cancer (NSCLC) and melanoma [ 21 , 22 , 23 , 24 , 25 , 26 ] has been less studied in RCC [ 27 , 28 , 29 ]. Moreover, current data on the impact of specific types of irAEs on outcomes are not entirely consistent.…”

Trial watch: STING agonists in cancer therapy

“… 167 , 169 , 170 The success of this regimen might have a particular positive impact on melanoma patients refractory to PD-1 blockers. 171 – 173 The PD-1 blocker nivolumab 174 is also being tested in combination with the STING agonist SB11285 in subjects with advanced solid tumors (NCT04096638). Only one clinical trial, enrolling patients with advanced solid tumors (NCT03956680), evaluated the safety and preliminary efficacy of ipilimumab and nivolumab together, 175 – 178 co-administered with the STING agonist BMS-986301.…”

From biomarkers to therapeutic targets: the promise of PD-L1 in thyroid autoimmunity and cancer

“…However, these confounding factors for recruitment and the latter classical “immortal time bias” can erroneously link better prognosis with the occurrence of irAE. That said, it should be acknowledged that a significant association between irAE and the ICI response persists after adjusting for potential confounders in a multivariable analysis 19 , 20 . Of interest, regardless of the affected organs (thyroid, skin, lung…), the presence or the treatment of irAEs does not require interruption or compromise ICI treatment 14 , 16 - 18 .…”