September 16, 2017
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Tocilizumab manages adverse events following PD-1 blockade therapy

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CHICAGO — Tocilizumab appeared to be a viable therapeutic option for patients with lung cancer who experienced an immune-mediated adverse event following treatment with PD-1 checkpoint blockade, according to study results presented at International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology.

Perspective from Heather Wakelee, MD

Despite their clinical benefit, immune checkpoint inhibitors can be associated with a variety of immune-mediated adverse events.

Corticosteroids are considered standard frontline treatment of these events, although the management of steroid-refractory events is poorly defined.

“There is a paucity of data on which consensus guidelines may be based,” Aparna Hegde, MD, chief research fellow at East Carolina University, said during the presentation. “Treatment with anti-IL-6 receptor monoclonal antibody, tocilizumab [Actemra, Genentech], led to improvement in systemic inflammatory response syndrome and immune-related adverse events in these patients. Hence, we adopted the use of tocilizumab as our standard of treatment for high-grade immune-related adverse events.”

Hegde and colleagues evaluated tocilizumab — an immunosuppressive drug — for the initial management of patients with immune-mediated adverse events following immune checkpoint inhibitor therapy for lung cancer treatment.

Among 87 patients treated with nivolumab (Opdivo, Bristol-Myers Squibb), 34 required treatment with tocilizumab (39.1%). These patients received 4 mg/kg tocilizumab IV over a 1-hour span.

All patients received corticosteroids (median dose, 60 mg prednisone equivalents).

Twenty-seven patients (79.4%) experienced clinical improvement, defined as resolution of symptoms or hospital discharge within 7 days. Median time to discharge was 4 days (range, 1-27).

At initial dose of tocilizumab, patients recorded a median C-reactive protein of 100.5 mg/L (range, 2-350.4).

Patients who received tocilizumab demonstrated no significant difference in median OS compared with patients who did not (6.1 months vs. 8.7 months).

The researchers noted a trend toward inferior OS among patients who required more than one dose of tocilizumab; however, this was not statistically significant (HR = 1.72; 95% CI, 0.87-3.37).

“Further multicenter randomized studies are needed to determine the definitive utility of tocilizumab and C-reactive protein as an accompanying biomarker in the management of high grade steroid-refractory immune-related adverse events,” Hedge said. – by Kristie L. Kahl

Reference:

Stroud CR, et al. Abstract OA03.05. Presented at: International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology; Sept. 14-16, 2017; Chicago.

Disclosure: Hegde reports no relevant financial disclosures.