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Background <p>The efficacy of immune checkpoint inhibitor (ICI) monotherapy on non-small-cell lung cancer (NSCLC) varies by <i>epidermal growth factor receptor</i> (<i>EGFR</i>) mutation subtypes. However, the impact of these subtypes on the clinical outcomes of chemoimmunotherapy (Chemo+ICI) or platinum-based chemotherapy (Chemo) in real-world practice remains unclear.</p> Objective <p>This study evaluated the impact of <i>EGFR</i> mutation subtypes on NSCLC treatment outcomes of Chemo and Chemo+ICI.</p> Patients and Methods <p>We retrospectively analyzed patients with advanced or recurrent <i>EGFR-</i>mutant NSCLC from 20 institutions between January 2017 and July 2022. Patients received Chemo with or without ICI after failure of EGFR-tyrosine kinase inhibitors. Common <i>EGFR</i> mutations were categorized as exon 19 deletions and exon 21 L858R mutations.</p> Results <p>Among the 403 patients, 205 (50.9%) had exon 19 deletions, and 198 (49.1%) had L858R mutations. For patients with L858R mutations, Chemo+ICI significantly improved progression-free survival (PFS) compared with Chemo (7.0 vs 5.3 months; <i>p</i> = 0.04). However, no significant difference in PFS was observed between treatments for patients with exon 19 deletions (6.7 vs 6.0 months; <i>p</i> = 0.96). Multivariate analysis identified Chemo+ICI as an independent predictor of PFS in patients with L858R mutations (hazard ratio 0.63; 95% confidence interval 0.43–0.92; <i>p</i> = 0.02).</p> Conclusions <p>Among patients with common <i>EGFR</i> mutation subtypes, those with L858R mutations demonstrated significantly improved PFS with Chemo+ICI than with Chemo. These findings suggest that Chemo+ICI may offer a more effective treatment option for patients with L858R-mutant NSCLC, warranting further investigation in prospective studies.</p>

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Impact of EGFR Mutation Subtypes on Response to Chemoimmunotherapy and Chemotherapy in Non-Small-Cell Lung Cancer After EGFR-TKI Failure

  • 期刊论文

  • 发表日期：

    2025年4月24日

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  • Kenji Morimoto,
  • Tadaaki Yamada,
  • Naoki Furuya,
  • Hisashi Tanaka,
  • Akihiro Yoshimura,
  • Tomohiro Oba,
  • Makoto Hibino,
  • Takahito Fukuda,
  • Yasuhiro Goto,
  • Akira Nakao,
  • Shinsuke Ogusu,
  • Yuta Okazaki,
  • Taishi Harada,
  • Takayo Ota,
  • Ken Masubuchi,
  • Koji Mikami,
  • Tae Hata,
  • Shoki Matsumoto,
  • Ryoichi Honda,
  • Koji Date,
  • Yusuke Chihara,
  • Hayato Kawachi,
  • Koichi Takayama

摘要

Background

The efficacy of immune checkpoint inhibitor (ICI) monotherapy on non-small-cell lung cancer (NSCLC) varies by epidermal growth factor receptor (EGFR) mutation subtypes. However, the impact of these subtypes on the clinical outcomes of chemoimmunotherapy (Chemo+ICI) or platinum-based chemotherapy (Chemo) in real-world practice remains unclear.

Objective

This study evaluated the impact of EGFR mutation subtypes on NSCLC treatment outcomes of Chemo and Chemo+ICI.

Patients and Methods

We retrospectively analyzed patients with advanced or recurrent EGFR-mutant NSCLC from 20 institutions between January 2017 and July 2022. Patients received Chemo with or without ICI after failure of EGFR-tyrosine kinase inhibitors. Common EGFR mutations were categorized as exon 19 deletions and exon 21 L858R mutations.

Results

Among the 403 patients, 205 (50.9%) had exon 19 deletions, and 198 (49.1%) had L858R mutations. For patients with L858R mutations, Chemo+ICI significantly improved progression-free survival (PFS) compared with Chemo (7.0 vs 5.3 months; p = 0.04). However, no significant difference in PFS was observed between treatments for patients with exon 19 deletions (6.7 vs 6.0 months; p = 0.96). Multivariate analysis identified Chemo+ICI as an independent predictor of PFS in patients with L858R mutations (hazard ratio 0.63; 95% confidence interval 0.43–0.92; p = 0.02).

Conclusions

Among patients with common EGFR mutation subtypes, those with L858R mutations demonstrated significantly improved PFS with Chemo+ICI than with Chemo. These findings suggest that Chemo+ICI may offer a more effective treatment option for patients with L858R-mutant NSCLC, warranting further investigation in prospective studies.