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PD-1 Inhibitor Efficacy Predicted By Immune-Related Adverse Events

Patients who experience immune-related adverse events during nivolumab or pembrolizumab monotherapy may have a higher chance of achieving an objective response than those who do not
30 Jan 2019
Immunotherapy;  Complications/Toxicities of Treatment
By Lynda Williams, Senior medwireNews Reporter

medwireNews: A review of advanced cancer patients in Spain suggests that immune-related adverse events (irAEs) may be a sign of treatment efficacy in patients using nivolumab or pembrolizumab. 

Overall, 56 different irAEs occurred in 37.7% of the 106 patients who were treated with either of the programmed cell death protein 1 (PD-1) inhibitors at the Hospital Universitario de la Princesa in Madrid, Spain, between January 2016 and August 2018. 

The most common irAE was hypothyroidism, affecting 19 patients at grades I–III, followed by nephritis affecting seven patients at grades I–III, and hyperthyroidism in six patients at grades I and II. Unacceptable toxicity halted treatment in nine patients with irAEs. 

A RECIST objective response rate (ORR) for the whole cohort was 41.5% but varied between 82.5% for the 40 patients with an irAE of any grade and 16.6% for the 66 patients without an irAE, giving a significant odds ratio (OR) of 23.5, report Ramon Colomer, from the institution, and colleagues.  

In addition, patients with an irAE had significantly longer progression-free survival (PFS) than those without (10 vs 3 months) and this was confirmed in multivariate analysis adjusting for a raft of confounding factors (hazard ratio=2.3). 

This was accompanied by a trend towards improved overall survival (OS) for patients who experienced irAEs, at 32 months versus 22 months, although this difference did not reach significance on multivariate analysis. 

The team explains that the patients were most commonly being treated for lung cancer (n=77), followed by melanoma (n=8), head and neck carcinoma (n=7) and renal carcinoma (n=5), with the remainder diagnosed with Hodgkin’s lymphoma, urothelial carcinoma, gallbladder adenocarcinoma, hepatocellular carcinoma or Merkel cell carcinoma. 

When only patients with lung cancer were assessed, irAEs were associated with a significantly improved ORR (OR=38.0) and PFS (10 vs 3 months) but again a nonsignificant difference in OS (26 vs 15 months), which the researchers say might be attributed to the short follow-up period of the study. 

Moreover, when the 29 patients with other types of tumours were grouped together, the ORR was again significantly better among those with than without an irAE, with an OR of 7.0, and there were trends to better PFS (10.5 vs 4.0 months), and OS (66.0 vs 33.0 months). 

“Our results confirm the suggestions of some previous studies performed with series that evaluated either number of pooled immune-therapy drugs or single tumour sites,” the researchers comment in the European Journal of Cancer

While admitting that their cohort’s heterogeneity could “be regarded as a limitation”, they believe it is “remarkable that the trend in ORR, PFS and OS was observed across all tumour types.” 

Ramon Colomer et al conclude: “Future studies of anti–PD-1 cancer immunotherapy should address this association to reveal the underlying biological mechanisms of efficacy.” 

Reference 

Rogado J, Sánchez-Torres JM, Romero-Laorden N, et al. Immune-related adverse events predict the therapeutic efficacy of anti–PD-1 antibodies in cancer patients. Eur J Cancer 2019; 109:21-27. DOI: https://doi.org/10.1016/j.ejca.2018.10.014

Last update: 30 Jan 2019

medwireNews (www.medwireNews.com ) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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