Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study

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2024年6月4日

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Tomoko Kobayashi,
Shintaro Iwama,
Ayana Yamagami,
Tetsushi Izuchi,
Koji Suzuki,
Koki Otake,
Yoshinori Yasuda,
Masahiko Ando,
Takeshi Onoue,
Takashi Miyata,
Mariko Sugiyama,
Daisuke Hagiwara,
Hidetaka Suga,
Ryoichi Banno,
Tetsunari Hase,
Naoki Nishio,
Shoichiro Mori,
Tomoya Shimokata,
Tomoyasu Sano,
Kaoru Niimi,
Nobuhisa Yoshikawa,
Shusuke Akamatsu,
Yuichi Ando,
Masashi Akiyama,
Michihiko Sone,
Makoto Ishii,
Hiroshi Arima

摘要

Background

Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI].

Methods

A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit.

Results

The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026].

Conclusions

The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.