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2018 Palliative Care: Immunotherapy-Related Adverse Events May Be More Common Than Initially Reported

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Key Points

  • The most common immune-related adverse outcome, hypothyroidism, occurred in 257 (9.2%) patients. Other side effects, such as thrombocytopenia, occurred in 5.7% of patients, and acute kidney injury occurred in 2.8% of patients.
  • Gastrointestinal and cardiac events were relatively rare.
  • KEYNOTE-24 reported that 0.6% of patients had hypophysitis, a rare condition involving acute or chronic inflammation of the pituitary gland, while this recent analysis found that 2.4% of patients experienced hypophysitis.

An analysis of nearly 2,800 patients with non­–small cell lung cancer (NSCLC) who received the immune checkpoint inhibitors nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq) found that adverse events may be more common than reported in the initial trials that led to the approval of these therapies. These findings will be presented by Cathcart-Rake et al at the upcoming 2018 Palliative and Supportive Care in Oncology Symposium (Abstract 184).

“Immunotherapy continues to be well tolerated, and severe side effects are less frequent than those seen with conventional chemotherapy. Still, immunotherapy can, in rare occasions, cause other serious medical problems,” said senior study author Elizabeth Jane Cathcart-Rake, MD, an oncology fellow at the Mayo Clinic, in a statement. “It’s important to understand the full extent of cancer treatments’ side effects, and patients and providers should be aware that it can take a while to fully assess them for newer therapies.”

About the Study

The researchers reviewed claims data from a large insurance database that listed adverse events due to immunotherapy. The database, OptumLabs Data Warehouse, was co-founded by the Mayo Clinic in 2012 and includes deidentified clinical data from more than 150 million people in the United States. The investigators determined if people received the programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors nivolumab, pembrolizumab, or atezolizumab between 2015 and 2017, and then looked at the frequency of immune-related adverse events.

Of 2,798 patients with NSCLC included in the study, 1,998 (71.4%) received nivolumab, 699 (25.0%) received pembrolizumab, and 101 (3.6%) received atezolizumab.

Most patients received standard forms of chemotherapy prior to their immunotherapy treatment.

“We believe that our study is the first to look at adverse events based on claims data, which gives a much broader, population-based perspective on outcomes than a single trial,” said Dr. Cathcart-Rake. “While there have been studies comparing data from multiple trials, our approach includes a comprehensive look at outcomes for most insured patients.”

The researchers were not able to account for people who do not have insurance, a potential limitation of the study.

Results

The most common immune-related adverse outcome, hypothyroidism, occurred in 257 (9.2%) patients. Other side effects, such as thrombocytopenia, occurred in 5.7% of patients, and acute kidney injury occurred in 2.8% of patients. Gastrointestinal and cardiac events were relatively rare.

Analyses of the data are ongoing so that researchers can obtain a better understanding of the absolute differences between trial reported toxicities and those seen in the population at large.

According to the authors, only about 14% of trials report adverse events at the time of publication. However, one trial, KEYNOTE-24, which compared pembrolizumab vs chemotherapy, allowed the authors to compare initial results with population-based data. KEYNOTE-24 reported that 0.6% of patients had hypophysitis, a rare condition involving acute or chronic inflammation of the pituitary gland, while this analysis found that 2.4% of patients experienced hypophysitis.

As a next step, the researchers may look at the timing of autoimmune side effects, which can be found in insurance-provider databases. If clinicians knew when side effects were most likely to occur, they may be able to intervene in a timely manner.

Disclosure: Study coauthor Aaron Scott Mansfield, MD, has a consulting or advisory role with Trovagene, Genentech, Bristol-Myers Squibb, and Abbvie, and receives institutional research funding from Novartis.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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