What Patients With Kidney Cancer Need to Know About Welireg

When a patient with kidney cancer asked her doctor about Welireg, she was pleasantly surprised with the results after receiving it.

When Maggie Cahill of Rockport, Massachusetts was faced with the possibility of a fourth partial nephrectomy, a surgical removal of part of the kidney, due to Von Hippel-Lindau-associated renal cell carcinoma, she instead asked her physician about Welireg (belzutifan), a drug she had learned about through social media word-of-mouth from fellow patients.

“The idea of the drug blew my mind, so it was at just knowing about it and knowing I was going to be going on, it was a big mental shift to be thinking that the possibility was that I'd be scanning and tumors would actually be shrinking,” said Cahill, now 51. “So that was the very first impact, processing it mentally and also preparing myself to go on it, I really just brought all my intention to it working as well. I mean, it works great. I think whether you bring your attention to it or not, it's a great drug.”

Welireg, according to the National Cancer Institute, is designed to inhibit the growth and survival of HIF-2alpha-expressing tumor cells.

The phase 3 LITESPARK-005 clinical trial, results of which were presented at the European Society for Medical Oncology (ESMO) Congress in 2023 before being published in August in The New England Journal of Medicine, showed that after a median of 25.7 months, patients treated with Welireg saw a 25% reduction in the risk of disease progression or death compared to those treated with Afinitor (everolimus), study chair Dr. Toni K. Choueiri told CURE in an interview.

Choueiri is the director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg professor of medicine at Harvard Medical School, both in Boston.

LITESPARK-005 enrolled 746 patients with metastatic clear cell renal cell carcinoma who had progressed following treatment with an immune checkpoint inhibitor and an anti-angiogenic therapy. The trial “establishes [Welireg] as a new treatment option” among this patient population, Choueiri and his colleagues wrote in the study.

Based on the results of LITESPARK-005, the Food and Drug Administration approved Welireg last year for the treatment of patients with advanced renal cell carcinoma (RCC) following treatment with a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).

In both the Welireg and Afinitor groups of the study, 99.2% of participants experienced at least one side effect, while 61.8% and 62.5%, respectively, experienced grade 3 (severe) to grade 5 (deadly) effects, with side effects leading to death in 13 and 19 patients, respectively.

“Overall, it doesn't have the same side effect profile of other treatments, it's a totally new side effect profile of a drug used in kidney cancer,” said Choueiri. “So anemia is a big one and hypoxia.”

Regarding anemia, or a low red blood cell count, 82.8% of patients treated with Welireg experienced it, with 32.5% of patients experiencing grade 3 or higher anemia. Hypoxia, or low oxygen level in the body’s tissues, was experienced by 14.5% of patients treated with Welireg, with 10.5% of patients in that group experiencing grade 3 or higher hypoxia.

“Those are the big ones that we need to pay attention to,” Choueiri said. “And we've been able to manage these side effects, sometimes by holding [off on a] drug, decreasing the dose, giving blood products, giving oxygen for hypoxia.”

Cahill, who will have been on Welireg for three years in October, said fatigue was the primary side effect she experienced from the drug.

“It took me a little while because I'm a pretty positive person, so to admit this to my deep bench [of a care team] there at Dana [-Farber Cancer Institute] and to say, ‘Actually, I'm kind of having a side effect that's impacting my life,’” Cahill said. “But once they saw the hemoglobin go low enough, combined with how I was presenting, they were like, ‘We're actually going to take you down a step,’ which I find kind of wonderful, how flexible we can be with the [Welireg], because the idea is, stay on it because it's shrinking things, but who knows What it's not allowing to grow in the first place.”

For patients with this disease type, it is very important to consult with their care teams, as Choueiri explained.

“These are new drugs. These are drugs that have particular side effects. These are unlike immune checkpoint inhibitors where I would say they were used in multiple indications outside kidney cancer, these are indications that are specific to kidney cancer,” he said. “So I think it's very important that folks are familiar with it. And just the approval was less than a year ago. So it's important also because these drugs, especially [Welireg], are being used in clinical trials. In first line and second line, in adjuvant, all this trial finished accrual. So if these trials are positive, but also different going to be approved earlier and earlier. So it's very important to know what's going on.”

“When you weigh having multiple surgeries against having a daily drug, the daily drug is going to be the thing that keeps your lifestyle closest to normal, if it can work,” Cahill said. “And [Welireg] just has an incredible track record of working with these kidney tumors.”

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