Highlights
- •In advanced cancer treated with anti–PD-1 antibodies nivolumab or pembrolizumab, incidence of irAEs was associated with a marked efficacy.
- •Response rate increased significantly from 16.6% to 82.5% when an irAE was present.
- •The follow-up showed an increase of PFS from 3 to 10 months when an irAE was present.
- •The follow-up showed an increase of OS from 22 to 32 months when an irAE was present.
Abstract
Background
Cancer immune therapy has shown remarkable benefit in the treatment of a range of
cancer types, although it may initiate autoimmune-related disorders in some patients.
We have attempted to establish whether the incidence of irAEs after the use of anti–PD-1
antibodies nivolumab or pembrolizumab in advanced malignancies is associated with
anti–PD-1 treatment efficacy.
Patients and methods
We studied patients treated with single-agent nivolumab or pembrolizumab for advanced
cancer. irAEs (immune-related adverse events) were identified clinically and graded
as per the Common Terminology Criteria for Adverse Events version 4.0. Efficacy was
evaluated with objective response rate (ORR, immune-Response Evaluation Criteria in
Solid Tumours [RECIST] criteria) progression-free survival (PFS) and overall survival
(OS). Tests were performed to determine the association between irAEs and ORR, PFS
or OS.
Results
We identified 106 patients. Primary diagnoses were lung cancer (n = 77), melanoma (n = 8), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma
(n = 1 each). IrAEs were observed in 40 patients (37.7%). The most frequent irAEs were
hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 44 patients (41.5%), and median PFS was
5.5 months (0.5–31 months). Thirty-three of the 40 patients with irAEs had objective
response (82.5%) in contrast with 11 of the 66 cases without irAEs (16.6%) (OR 23.5,
P < 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without
irAEs (HR 2.2, P = 0.016). OS in patients with irAEs was 32 months and 22 in those without irAEs,
without statistically significant differences.
Conclusion
In advanced cancer treated with single-agent anti–PD-1 antibodies, patients with irAEs
showed a markedly improved efficacy over patients without irAEs (ORR of 82.5% and
PFS of 10 months vs ORR of 16.6% and PFS of 3 months). Future studies of anti–PD-1
immune-therapy should address this association to explore the underlying biological
mechanisms of efficacy.
Keywords
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Article info
Publication history
Published online: January 22, 2019
Accepted:
October 22,
2018
Received in revised form:
October 19,
2018
Received:
June 21,
2018
Identification
Copyright
© 2018 Elsevier Ltd. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Immune-related adverse events predict the therapeutic efficacy of pembrolizumab in urothelial cancer patientsEuropean Journal of CancerVol. 116
- PreviewWe read with great interest the article published in the European Journal of Cancer by Rogado et al. [1], ‘Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients’. They clearly showed the relationship between the occurrence of immune-related adverse events (irAEs) and the efficacy of anti–programmed death receptor 1 (PD-1) antibodies in various types of tumours. Recently, we have had similar results in a single tumour type, urothelial cancer.
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