Real-world data highlight tofacitinib potential for irAE management in cancer patients

In a study presented at ESMO Asia 2023, tofacitinib, a rapidly acting JAK-STAT inhibitor with reported efficacy in the treatment of various autoimmune diseases, was effective for the management of difficult-to-treat immune-related adverse events (irAEs) and was well-tolerated in cancer patients, with only a few patients developing infectious events.

“The treatment strategy against irAEs induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents,” said Dr Qing Liu from the Zhongshan Hospital Fudan University, Shanghai, China, at ESMO Asia 2023.

“[H]ighly unselective immunosuppressive agents [such as steroids] have important side effects that may jeopardize immune response to cancer,” noted Dr Marco Donia from the Copenhagen University Hospital, Herlev-Gentofte, Copenhagen, Denmark, in a press release.

Liu and team retrospectively evaluated 53 cancer patients (mean age 65 years, 62 percent male) from six institutions who received ICIs and tofacitinib treatment for the management of irAEs. When participants were categorized according to clinical severity and steroid responsiveness, most were steroid-resistant (n=30), 11 had life-threatening cases, while 12 had steroid taper failure. [ESMO Asia 2023, abstract 433MO]

Median time from irAE onset to tofacitinib initiation was 17.0 days. Median duration of tofacitinib treatment was 48.5 days.

All 12 patients who had steroid taper failure underwent clinical remission. The corresponding rates in the subgroups of patients with steroid resistance and life-threatening consequences were 96.7 percent and 54.5 percent, respectively.

In four patients who developed infectious events, tofacitinib was well-tolerated.

During a median follow-up of 21.4 months, median progression-free survival was 5.6 months and median overall survival was 16.1 months.

Did not compromise immune response

“[The findings] are particularly interesting, as we are constantly looking for agents [with] a more targeted action than steroids and … a lower impact on immune response to cancer,” Donia said.

Tofacitinib did not compromise the antitumour efficacy of immunotherapy, underscored Liu. “Tofacitinib showed promising clinical efficacy in patients experiencing irAEs, particularly in patients who failed to respond to steroid or experienced failure during steroid tapering.”

“The high rates of irAE remission seen in patients with steroid resistance were encouraging,” pointed out Donia. To put into context, all but one of the 30 steroid-resistant patients underwent clinical remission.

Favourable safety profile

“Moreover, and most importantly, tofacitinib exhibited a favourable safety profile in cancer patients developing irAEs in terms of both toxicity and antitumour activity,” said Liu.

The most common irAE was myocarditis (n=48). Tofacitinib treatment led to a continuous reduction in relative cardiac troponin T levels in patients with ICI-related myocarditis in the steroid-resistant and steroid taper failure subgroups. However, Liu noted that the effect was not as clear in the life-threatening subgroup.

She added that irAE management must be guided by clinical severity and steroid sensitivity and called for future prospective studies to better support their findings.

“I agree that the real-world evidence presented, coupled with previous case reports, warrant prospective studies,” echoed Donia.