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Treatment-related adverse events and response rate to immune checkpoint inhibition
Yanmin Li1, Zhengping Wang2, Ting Guo3
1Department of Urology, First Affiliated Hospital of Gannan Medical University, Ganzhou, PR China.
Background:
Immune checkpoint inhibition (ICI) represents a novel treatment modality for refractory cancers, and improving prediction of potential responders is critical.
Method:
We hypothesized that ICI is a systemic-effecting mechanism. The objective response rate (ORR) for anti-PD-1, anti-PD-L1, anti-CTLA-4, or combination therapy was plotted against the corresponding all-grade and grade 3-4 (G3/4) treatment-related adverse events (TRAEs) across several cancer types using an extensive literature search (MEDLINE and Google Scholar; December 1, 2012-December 30, 2017).
Results:
Sixty-six eligible studies comprised 76 cohorts and 25 cancer types. A significant correlation was present between all-grade or G3/4 TRAEs and the ORR. The correlation coefficient was 0.5 for all-grade and 0.4 for G3/4 TRAEs, suggesting that >50% of the differences in the ORR across cancer types may be reflected by TRAEs and 40% of ORR differences may be predicted by G3/4 TRAEs. Hodgkin's lymphoma and Merkel cell carcinoma showed a better response, while adrenocortical cancer, breast cancer, and uveal melanoma showed a worse response, compared with that predicted by TRAE.
Conclusion:
There is a strong relationship between TRAEs and ICI activity across multiple cancers. The toxicity profile compared with the ORR to ICIs should be investigated in phase I trials.
Insights
Immune checkpoint inhibition (ICI) shows a strong link between treatment-related adverse events (TRAEs) and objective response rates (ORR) across many cancers. Toxicity profiles can help predict ICI effectiveness and guide future clinical trials.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trial Analysis
Background:
- Immune checkpoint inhibition (ICI) offers a new treatment for difficult cancers.
- Predicting patient response to ICI is crucial for effective cancer therapy.
Purpose of the Study:
- To test the hypothesis that ICI has systemic effects.
- To correlate objective response rates (ORR) with treatment-related adverse events (TRAEs) for ICI therapies.
Main Methods:
- Literature search of MEDLINE and Google Scholar (2012-2017).
- Analysis of ORR for anti-PD-1, anti-PD-L1, anti-CTLA-4, or combination therapies.
- Correlation of ORR with all-grade and grade 3-4 TRAEs across 25 cancer types.
Main Results:
- 66 studies and 76 cohorts were analyzed.
- Significant positive correlation found between TRAEs and ORR (r=0.5 for all-grade, r=0.4 for G3/4).
- TRAEs may explain over 50% of ORR variations; G3/4 TRAEs may predict 40% of ORR differences.
Conclusions:
- A strong relationship exists between TRAEs and ICI efficacy across diverse cancers.
- Toxicity profiles should be evaluated alongside ORR in Phase I trials for ICI.
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