Lunch & Poster Display session Poster Display session

52P - Chronic and late-onset toxicities from immune checkpoints inhibitors (ICIs): Analysis of the publications leading to ICIs approval between 2011 and 2019

Presentation Number
52P
Lecture Time
12:15 - 12:15
Speakers
  • E. Ghisoni (Candiolo, (TO), Italy)
Session Name
Lunch & Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
12:15 - 13:15
Authors
  • E. Ghisoni (Candiolo, (TO), Italy)
  • L. Marandino (Candiolo, Italy)
  • G. Valabrega (Candiolo, Italy)
  • M. Aglietta (Candiolo, (TO), Italy)
  • M. Di Maio (, Italy)

Abstract

Background

Immune checkpoints inhibitors (ICIs) are receiving approval for a growing number of indications. Even if generally well-tolerated, ICIs can cause rare but severe immune-related adverse events (irAEs) with late onset and long-term impact. Aim of this analysis was to evaluate the completeness of irAEs description, with particular attention to irAEs duration and occurrence of late toxicities, in ICIs pivotal trials.

Methods

We analysed the publications corresponding to the studies leading to ICIs approval by US Food and Drug Administration (FDA) and/or European Medicines Agency from March 2011 up to August 2019. We searched for duration of follow-up, proportion of patients still on treatment at data cut-off, duration of irAEs and proportion of patients with unresolved toxicities at data cut-off.

Results

Overall, we found 58 publications, corresponding to 49 trials (table). Among all studies, median follow-up was 13,5 months (interquartile range [IQR] 5,8–14,9), and it was 10,2 months (IQR 5 -11,9) for the ones which led to ICIs approval with FDA fast-track procedure versus 15,2 months (IQR 12-16,2) for those leading to ICIs approval through regular procedure (p < 0.001). In 40/58 publications (68,9%), a mean of 22,4% of patients (range 1%-63%) were still ongoing at data cut-off; in 10/58 (17,2%) data were not reported. Duration of irAEs and proportion of patients with unresolved toxicities at data cut-off were not specified in 52 publications (89,6%). In 6 publications with available data, 3% to 66% of patients had still ongoing irAEs. Secondary publications were available in 15/58 cases (25,8%) and showed that even at longer follow-up (median 24.2 months), the proportion of patients still on treatment at data cut-off was not negligible (7.3%-32%) and only 3/15 studies (20%) presented an update regarding duration of irAEs.

Table: 52P

Publications n (%)Studies with patients ongoing at data cut-off n (%)Median follow-up monthsStudies reporting duration of irAEs n (%)
Whole series5840 (81)13.56 (10.3)
Year of publication 2010 2015 2016 2017 2018 2019 1 (1.7) 11 (18.9) 5 (8.6) 21 (36.2) 15 (25.8) 5 (8.6) n.a. 3 (27.2) 5 (100) 17 (80.9) 13 (86.6) 3 (60) 27.8 13.1 10.4 14 12.9 11.1 1 (100) 3 (27.2) 0 1 (4.7) 1 (7.6) 0
Drug Pembrolizumab Nivolumab Atezolizumab Avelumab Durvalumab Ipilimumab Nivolumab + Ipilimumab 29 (50) 12 (20.6) 7 (12) 3 (5.2) 2 (3.5) 2 (3.5) 3 (5.2) 18 (62) 9 (75) 6 (85.7) 3 (100) 2 (100) n.a. 3 (100) 10.6 9.5 14.5 13.4 10.1 30.3 18.7 0 3 (20) 0 0 0 2 (100) 1 (33.3)
Studies leading to FDA fast-track approval24 (41.4)23 (95,8)10.22 (6)

n.a.: not available data

Conclusion

Description of toxicity in publications of clinical trials of ICIs is often suboptimal especially in terms of duration and long-term sequelae. Future efforts should focus on capturing the real impact of irAEs on patients’ QoL to better define treatments value.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G. Valabrega: Honoraria (self): Roche; Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): PharmaMar; Honoraria (self): Tesaro. M. Aglietta: Honoraria (self): Tesaro; Honoraria (self): Roche; Honoraria (institution): AstraZeneca. M. Di Maio: Honoraria (institution): Tesaro; Honoraria (self): Bristol Meyers Squibb; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Takeda; Honoraria (self): Janssen. All other authors have declared no conflicts of interest.

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