Immune-related AEs linked to PD-1 inhibitor efficacy
medwireNews: The development of immune-related adverse events (irAEs) is associated with better outcomes in response to programmed cell death protein 1 (PD-1) inhibitor monotherapy across a range of tumour types, suggests a chart review.
Among 106 Spanish patients with metastatic cancer, the 37.7% who developed irAEs of any grade (most frequently hypothyroidism) were significantly more likely to achieve a response to treatment with either single-agent nivolumab or pembrolizumab than the 62.3% who did not, with objective response rates (ORRs) of 82.5% and 16.6%, respectively.
Median progression-free survival (PFS) was similarly significantly better among patients with irAEs, at 10 months versus 3 months for those without irAEs. This association remained significant on multivariable analysis adjusting for factors such as age, sex and histology, such that individuals who developed irAEs were a significant 2.3-fold more likely to survive without progression.
Overall survival (OS) was also numerically higher in participants with versus without irAEs, at 32 and 22 months, respectively, but this did not reach statistical significance, which the researchers believe could be due to the short follow-up, at a median of 6 months.
Although the majority of patients included in the study had lung cancer (n=77), the rest had a variety of malignancies, including melanoma in eight patients, head and neck carcinoma in seven, renal cell carcinoma in five, Hodgkin’s lymphoma and urothelial carcinoma in three patients each, and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma in one each.
The findings were similar in the lung cancer and non-lung cancer groups, with the exception that the association between irAEs and improved PFS was not statistically significant in the non-lung cancer group.
Ramon Colomer and the team from Hospital Universitario la Princesa in Madrid, Spain, say in the European Journal of Cancer that “it is remarkable that the trend in ORR, PFS and OS was observed across all tumour types included in our series.”
The authors continue: “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.”
But they highlight the need for future research “to explore the underlying biological mechanisms of efficacy.”
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