Side Effects From Immune Checkpoint Inhibitors may be More Common Than Thought

By Megan Brooks

NEW YORK (Reuters Health) - Immune-related side effects with immune checkpoint inhibitors may be more common than reported in the initial trials that led to their approval, according to a review of claims data.

That's not surprising, senior author Dr. Elizabeth Jane Cathcart-Rake of the Mayo Clinic in Rochester, Minnesota, noted in a phone interview with Reuters Health.

"Clinical trials are really well-defined studies and follow patients for a finite period of time and have more stringent entrance criteria. So we do tend to miss some adverse events in trials," she explained. "Clinically, we've been seeing immune-related adverse events pretty commonly. It's still a small risk but I'm not surprised the numbers are a bit higher than originally reported."

Dr. Cathcart-Rake will present her findings November 17 during the 2018 Palliative and Supportive Care in Oncology Symposium in San Diego, California.

The Mayo Clinic team reviewed claims data for 3,164 patients with non-small cell lung cancer (NSCLC) who were treated with PD-1 or PD-L1 checkpoint inhibitors nivolumab, pembrolizumab, or atezolizumab.

The claims data showed immune-related adverse events (irAEs) in nearly a quarter of patients (24.1%) overall. Of note, frequencies of hypophysitis and pneumonitis were higher than that seen in pivotal clinical trials.

For example, in KEYNOTE-024 and KEYNOTE-042 (comparing pembrolizumab vs. chemotherapy), rates of hypophysitis were 0.6% and 0.5%, versus 2.8% in the claims data. Rates of pneumonitis in these two trials were 5.8% and 8.3%, respectively, versus 10.9% in the claims data.

The rate of hypothyroidism was lower than in KEYNOTE-024 and 042 compared with claims data (9.1% and 12.1% vs. 7.0%).

Preliminary multivariate logistic modeling data suggested significantly higher frequencies of irAEs in Hispanics (odds ratio, 1.44) and significantly lower frequencies when PD-L1 agents are used second line (OR, 0.71).

"Immunotherapy continues to be well tolerated, and severe side effects are less frequent than those seen with conventional chemotherapy," Dr. Cathcart-Rake said in a news release from the American Society of Clinical Oncology (ASCO). "Still, immunotherapy can, in rare occasions, cause other serious medical problems. 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."

Claims data complement clinical-trial data and allows for a broader view of the frequency of adverse events, Dr. Cathcart-Rake told Reuters Health. She said it's important for clinicians to counsel patients and primary-care providers on immune-related AEs. Close clinical monitoring and early treatment of irAEs is equally important, she added.

SOURCE: https://pallonc.org/

2018 Palliative and Supportive Care in Oncology Symposium.

(c) Copyright Thomson Reuters 2018. Click For Restrictions - https://agency.reuters.com/en/copyright.html

For more Pharmacy Learning Network articles, visit the homepage

To learn about Pharmacy Learning Network Live meetings, click here