Immune-related AEs linked to improved outcome on anti-PD-1 therapy
medwireNews: Patients who develop immune-related adverse events (irAEs) while receiving anti-programmed cell death protein 1 (PD-1) antibodies for advanced cancer have a substantially greater treatment response than those with no such events, say researchers.
Specifically, Ramon Colomer and team, from Hospital Universitario de la Princesa in Madrid, Spain, found that the development of irAEs was associated with a 23.5-fold increased likelihood for an objective response.
The results are based on a medical record review of all 106 patients (mean age 69 years, 72% men) with advanced metastatic cancer who were treated with single-agent nivolumab (3 mg/kg every 14 days) or pembrolizumab (first-line: 200 mg every 21 days, second-line 2 mg/ kg every 21 days) at the authors’ institute between January 2016 and August 2018.
During this time, 40 (37.7%) patients experienced irAEs, most commonly hypothyroidism (n=15), nephritis (n=5), and hyperthyroidism (n=4).
Overall, the objective response rate (ORR) was 41.5% and the median progression-free survival (PFS) time was 5.5 months.
However, the ORR increased to 82.5% and median PFS increased to 10 months among the patients with irAEs, with both outcomes significantly better than those observed among the patients who did not develop irAEs, at 16.6% and 3 months, respectively, after adjustment for a number of potential confounders such as age, sex, histology, smoking status, and prior treatment.
Overall survival was also longer among the patients with irAEs than among those without irAEs, at 32 versus 22 months, but the difference was not statistically significant, possibly due to the short follow-up period, say the researchers.
Colomer et al note that the results were similar when they analyzed the data according to tumor type, namely lung cancer (n=77 cases) and non-lung cancer (n=29), which included eight melanomas, seven head and neck carcinomas, five renal carcinomas, three Hodgkin lymphomas, three urothelial carcinomas, and one case each of gallbladder adenocarcinoma, hepatocellular carcinoma, and Merkel cell carcinoma.
Similar results were also observed regardless of the degree of PD-L1 expression and whether or not a patient had received radiotherapy.
Writing in the European Journal of Cancer, the investigators describe their findings as “remarkable” given that the study included patients with several different types of cancer, receiving different lines of just one type of immune checkpoint inhibitor – anti-PD-1 antibodies.
They say: “Our results confirm the suggestions of some previous studies performed with series that evaluated either [a] number of pooled immune-therapy drugs or single tumour sites.”
Colomer and co-authors conclude that future studies should “explore the underlying biological mechanisms of efficacy” with regard to irAEs and anti-PD-1 immune therapy.
By Laura Cowen
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