Thyroid Immune-Related Adverse Events More Likely in Renal Cell Cancer

Zoe Quandt, MD, MS

Thyroid immune-related adverse events were more common in certain types of cancers than others and were more prevalent in the real world than in clinical trials, according to new research to be presented at the Endocrine Society (ENDO) 2020 Annual Scientific Sessions.

Zoe Quandt, MD, MS, and colleagues from the University of California San Francisco used electronic health record (EHR) data to identify patients who developed thyroid dysfunction after immune checkpoint inhibitors to estimate the real-world incidence of immune-related adverse events. The team found evidence that renal cell cancer gave patients a higher risk of thyroid immune-related adverse events—even after adjustment for immune checkpoint inhibitor exposure.

Quandt, a Clinical Fellow at the University of California San Francisco School of Medicine, and the investigative team collected data from the EHR of a US academic center. The team identified patients who were treated with immune checkpoint inhibitors between 2012-2018. Patients were excluded if they had thyroid cancer or pre-existing thyroid disease.

The investigators defined thyroid dysfunction as a thyroid-stimulating hormone level >10, an abnormal-free T4, or a prescription for thyroid hormone replacement or anti-thyroid medication.

Overall, Quandt and the team assessed 1146 patients who did not have a pre-existing thyroid disease and received immune checkpoint inhibitors. The most common treatment was pembrolizumab (45%), then nivolumab (20%). Other patients (<10%) received atezolizumab; durvalumab; ipilimumab monotherapy; combined ipilimumab/nivolumab; or other immune checkpoint inhibitor combinations.

The most common cancer treated was melanoma in 32% of patients, followed by non-small cell lung cancer (13%). Other cancer prevalence was <10% each.

Less than 20% of patients developed a thyroid immune-related adverse event.

The cancer type was significantly associated with new onset thyroid dysfunction (P=.01). Rates of adverse events ranged from 10% I glioblastoma to 40% in renal cell cancer.

There was no significant link between adverse events and specific immune checkpoint inhibitors, but adverse events were more common in patients who received a combination of ipilimumab and nivolumab (31%) compared to pembrolizumab (18%, P=.03), nivolumab (18%, P <.01), and ipilimumab (15%, P=.02).

Treatment with immune checkpoint inhibitors is an important step in treating certain cancers and has the potential to offer patients sustained remissions. The drugs take the brakes off the immune system so it can recognize and attack cancer cells.

But with the treatment can come adverse events and the immune system could attack normal, noncancerous cells. Abnormal thyroid levels, particularly hypothyroidism, is 1 of the more common side effects. Investigators could not see the extent of hypothyroidism outside of trial settings, which prompted the collection of data from the EHR to learn more about how common the effect was in practice.

“Understanding who gets these immune-related adverse events, why they get them, and what impact they have on response to therapy is an essential part of optimizing our use of immune checkpoint inhibitors,” Quandt said in a statement.

The findings should educate clinicians and patients alike about the risks.

Additional research could focus on the reasons for the different rates of adverse events among different cancers and the effect on outcomes.

The study, “Finding the Needles in the Haystack: Harnessing the Electronic Health Record to Find Thyroid Immune Related Adverse Events,” will be presented at the Endocrine Society (ENDO) 2020 Annual Scientific Sessions.