irAEs linked to SCLC immunotherapy clinical benefit
medwireNews: The development of immune-related adverse events (irAEs) is associated with improved clinical outcomes in response to immune checkpoint blockade in patients with small-cell lung cancer (SCLC), suggests a chart review.
“These findings have implications for counseling patients who may develop irAEs if these events are confirmed to be correlative biomarkers of efficacy in SCLC,” presenting author Biagio Ricciuti (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) told delegates at the IASLC World Conference on Lung Cancer 2019 in Barcelona, Spain.
He explained that irAEs have been associated with immunotherapy outcomes in the non-small-cell lung cancer and melanoma settings, but whether such a correlation exists in SCLC remains unknown.
The team therefore analyzed data from 183 individuals who received treatment with at least one dose of an anti-PD-1 or anti-PD-L1 agent, either as monotherapy (59.6%) or together with a CTLA-4 inhibitor (40.4%), at one of six US institutions between 2014 and 2018.
irAEs of any grade developed in 39.9% of patients, most commonly gastrointestinal (14.7%) and respiratory (12.0%) irAEs, while events of grade 3 or 4 occurred in 17.5%. The median time to onset of irAEs was 24 days.
Individuals who experienced at least one irAE were significantly more likely to respond to immunotherapy than their counterparts who did not develop irAEs, with objective response rates of 27.4% and 3.6%, respectively.
Progression-free survival was also significantly improved in patients with versus without irAEs, at a median of 3.8 versus 1.3 months, giving a hazard ratio (HR) for progression or death of 0.31, as was overall survival, at a median of 13.8 versus 2.9 months, and an HR for death of 0.33.
These results were confirmed in a multivariate analysis adjusting for brain metastases, age, sex, ECOG performance status, and immunotherapeutic regimen, with an HR for progression or death of 0.46 and for death of 0.47.
In conclusion, Ricciuti stressed that “further studies are needed to validate our findings and to determine whether specific irAEs are associated with benefit from immunotherapy.”
Discussing the presentation, Herbert Loong, from The Chinese University of Hong Kong, noted that it would be “worthwhile to further dissect this data.” Specifically, it would be interesting to know the number of patients who had one versus more than one irAE, and whether the outcomes are even better for those who develop multiple irAEs, he said.
Loong added that it would also be useful to have data on the use of steroids and tumor necrosis factor inhibitors for the management of irAEs, and to investigate their association with response and survival outcomes.
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