Immune-Related Adverse Events Improve Overall Response Rate Following Cancer Immunotherapy

By Jeff Craven /alert Contributor
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Patients with advanced cancer receiving anti-PD-1 immunotherapy who go on to have an immune-related adverse event may have better overall response rates to treatment than those patients who did not develop an immune-related adverse event, recent research from the ASCO meeting in Chicago.

“In our clinical practice, a number of lung cancer patients receiving anti-PD-1 antibodies in whom we had to delay or discontinue therapy because of severe immune related adverse events (irAEs), showed a striking persistence of the clinical response even after discontinuing immunotherapy,” Jacobo Rogado Revuelta, MD, from Hospital Universitario Infanta Leonor in Madrid, Spain, told MD /alert. “We wanted to investigate the degree of this association, and whether it could be generalized to all cancer types.”

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In a retrospective review, Rogado Revuelta and colleagues evaluated 110 patients who received nivolumab or pembrolizumab between January 2016 and September 2018. They graded irAEs using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and measured efficacy with progression-free survival (PFS), overall survival (OS) and overall response rate (ORR). The most common advanced cancer was lung cancer in 78 patients followed by melanoma in 10 patients, head and neck carcinoma in 7 patients, renal carcinoma in 5 patients, Hodgkin’s lymphoma in 3 patients, urothelial carcinoma in 3 patients, and hepatocellular carcinoma, gastric adenocarcinoma, gallbladder adenocarcinoma and Merkel cell carcinoma in 1 patient each.

“Our study concluded that in advanced cancer of any type treated with the anti-PD-1 antibodies nivolumab or pembrolizumab, patients who developed irAEs of any degree obtained, in comparison with patients without irAEs, a very significantly improved efficacy in terms of both response rate and progression-free survival,” Rogado Revuelta said. “This effect strongly suggests that both efficacy and adverse effects occur though the same mechanism of action.”

Overall, 40 patients (36.4%) experienced an adverse event, and the most frequent consisted of hypothyroidism in 15 patients, nephritis in 5 patients and hyperthyroidism in 4 patients.

There was an objective response in 45 patients (40.9%), with 33 of 40 patients in the irAEs group having an objective response (82.5%) compared with 12 of 70 patients (17%) who did not have an irAE (odds ratio, 22.78; 95% confidence interval, 5.9-87.0; P < .000001). The median PFS was 5 months (0.5 months-32 months) and the median overall survival was 24.5 months (3 months-110 months). In patients with irAEs, the PFS was 10 months compared with patients who did not experience irAEs (hazard ratio, 2.4; P = .004). irAE patients also showed a greater OS at 32 months compared with non-irAE patients at 22 months, but the difference was not statistically significant.

“It is important for practicing oncologists to recognize that those patients with advanced cancer receiving immunotherapy that develop irAEs have a higher probability of obtaining a good clinical outcome, even when they receive corticosteroids (that are given to treat the irAEs) or in those cases that discontinue treatment, so clinicians have to be patient when an irAE occurs and follow the established treatment guidelines with confidence,” Rogado Revuelta said in the interview.

Revuelta JRR, et al. Abstract e14064. ASCO 2019 Annual Meeting; May 31-June 4; Chicago, IL.