Association of immune-related adverse events with durvalumab efficacy after chemoradiotherapy in patients with unresectable Stage III non-small cell lung cancer

期刊论文
发表日期：

2024年3月22日

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Koji Haratani,
Atsushi Nakamura,
Nobuaki Mamesaya,
Kenji Sawa,
Yoshimasa Shiraishi,
Ryota Saito,
Junko Tanizaki,
Yosuke Tamura,
Akito Hata,
Kosuke Tsuruno,
Tomohiro Sakamoto,
Shunsuke Teraoka,
Masahide Oki,
Hiroshi Watanabe,
Takaaki Tokito,
Kenji Nagata,
Takeshi Masuda,
Yasushi Nakamura,
Kazuko Sakai,
Yasutaka Chiba,
Akihiko Ito,
Kazuto Nishio,
Nobuyuki Yamamoto,
Kazuhiko Nakagawa,
Hidetoshi Hayashi

摘要

Background

Immune-related adverse events (irAEs) have been found to predict PD-L1 inhibitor efficacy in metastatic NSCLC. However, the relation of irAEs to clinical outcome for nonmetastatic NSCLC has remained unknown.

Methods

In this multicenter prospective study of Stage III NSCLC treated with PACIFIC regimen, the relation of irAEs to PFS was evaluated by 8-week landmark analysis to minimise lead-time bias as well as by multivariable analysis adjusted for baseline factors. irAEs were categorised as mild or nonmild according to whether they were treated with systemic steroid.

Results

Median PFS was 16.0 months, not reached, and 9.7 months for patients without (85 cases) or with mild (21 cases) or nonmild (21 cases) irAEs, respectively. Multivariable analysis indicated that nonmild irAEs were associated with poor PFS, with HRs of 3.86 (95% CI, 1.31–11.38) compared with no irAEs and 11.58 (95% CI, 2.11–63.63) compared with mild irAEs. This pattern was consistent after irAE grade, the number of durvalumab doses and immune profiles (PD-L1 score, CD8⁺ tumour-infiltrating lymphocyte density, and tumour mutation burden) were taken into consideration.

Conclusions

The development of mild irAEs might predict a better survival outcome, whereas immunosuppressive steroid–treated irAEs were associated with a worse outcome, regardless of baseline clinical and immune profiles.