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Immunotherapy-related toxicities may be more common than reported in trials



– Certain immune-related adverse events related to PD1/PD-L1 treatment of patients with non–small cell lung cancer (NSCLC) may be more common than reported in clinical trials, a recent analysis of administrative claims data suggests.

Pneumonitis was seen in 10.9% of patients up to 60 days after the last dose of immunotherapy, according to the analysis of data from a large, U.S. commercial insurance database, presented at the Palliative and Supportive Care in Oncology Symposium.

By comparison, pneumonitis was reported in just 5.8% of NSCLC patients during treatment with the PD-1 (programmed cell death-1) inhibitor pembrolizumab in KEYNOTE-024, a pivotal randomized phase 3 clinical trial, said Elizabeth Jane Cathcart-Rake, MD, senior study author and an oncology fellow at the Mayo Clinic, Rochester, Minn.

Rates of immune-related adverse events in this study were generally higher than in clinical trials, both for common side effects and more rare conditions such as hypophysitis, according to Dr. Cathcart-Rake.

These new claims-based data might be considered complementary to clinical trial data, the researcher said.

“Together, they may give us a better sense of the broader implications of these adverse events,” she said in an interview.

Joe Rotella, MD, a board member of the American Academy for Hospice and Palliative Care Medicine, said results of this insurance database study provide a perspective on the real-world incidence of adverse events associated with immune checkpoint inhibitors.

“We’ve only been using these therapies for a few years, so this new analysis gives us more information on the prevalence of these side effects in patients as the therapies gain wider use,” Dr. Rotella said in a news release.

In the study, Dr. Cathcart-Rake and coinvestigators queried the OptumLabs Data Warehouse to identify 3,164 patients with NSCLC who received PD-1 or PD-L1 (programmed death-ligand 1) inhibitors between 2015 and 2017. They looked at incidence of adverse events both at the time of the last immunotherapy dose and at 60 days after the last dose.

The incidence of pneumonitis, just 4.9% on the last date of immunotherapy, increased to 10.9% at 60 days after the last dose, Dr. Cathcart-Rake reported.

Beyond pneumonitis, the most common immunotherapy-related toxicities at 60 days were hypothyroidism in 7.0%, arrhythmia in 6.1%, and nephritis or acute kidney injury in 5.4%, according to the investigators.

Dr. Cathcart-Rake also highlighted the incidence of some less common immunotherapy-related toxicities such as hypophysitis or hypothalamic-pituitary-adrenal axis toxicity, seen in 2.8% of patients by 60 days.

“That’s a small number, but hypophysitis can be really profound, and frequently leads to hospitalization,” she said. “I think this just gives us enough of a signal that providers really need to be on top of looking for these adverse events and to counsel patients beforehand.”

These data could also be helpful for advising hospitalists, emergency room physicians, and other providers who may not be attuned to the potential risks of cancer immunotherapy as compared with traditional cytotoxic chemotherapy, Dr. Cathcart-Rake said at the meeting cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

“A patient with cancer may be on immunotherapy and their risk for infection is quite low, but they may be at a huge risk for pneumonitis, which is treated completely differently,” she said. “So I think this should just raise alarms that close clinical monitoring for these conditions is really important.”

Dr. Cathcart-Rake disclosed that her institution receives research funding from Novartis. One study coinvestigator reported consulting or advisory roles with Trovagene, Genentech, Bristol-Myers Squibb, and Abbvie.

SOURCE: Cathcart-Rake EJ et al. 2018 Palliative and Supportive Care in Oncology Symposium. Abstract 184.

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