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Background <p>LCNEC is a rare high-grade neuroendocrine malignancy with poor prognosis and limited evidence to guide systemic therapy.</p> Methods <p>Prospective, single-arm phase II study of 1st-line durvalumab 1500&#xa0;mg + cisplatin or carboplatin and etoposide (EP) q3 weeks for 4 cycles, followed by durvalumab 1500&#xa0;mg q4 weeks, in aLCNEC. The primary endpoint was 12-month PFS (RECIST v1.1, radiologist-assessed); secondary endpoints were ORR, OS, and safety. Sample size followed a single-stage Fleming design (one-sided α = 0.10, power 80%) testing a 12-month PFS rate ≤ 5% (H0) <i>vs</i> ≥ 18% (H1). The study closed early due to slow accrual after twelve of twenty-two planned patients were enrolled.</p> Results <p>Twelve patients were treated (median age 68y; 66.7% male; 91.7% smokers; 91.7% stage IVB). After median follow-up of 12.8&#xa0;months (95% CI 8.5–21.3), 92% had progressed and 75% had died. Median PFS was 4.4&#xa0;months (95% CI 3.1–12.9); 12-month PFS was 25.0% (95% CI 6.0–50.5), exceeding the ≤ 5% null hypothesis (H0) and compatible with the ≥ 18% target (H1). Median OS was 12.8&#xa0;months (95% CI 5.2–NR); 12-month OS was 58.3% (95% CI 27.0–80.1). ORR was 50.0%, and DCR was 91.7%. All three patients with untreated brain metastases achieved complete intracranial response. Toxicities were mainly grade 1–2; 41.7% had grade 3 adverse events; three discontinued durvalumab for immune-related toxicity; and no treatment-related deaths occurred.</p> Conclusions <p>This first prospective evaluation of durvalumab + EP in aLCNEC, though underpowered, demonstrates efficacy and safety consistent with design expectations.</p>

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Phase II study of 1st-line durvalumab and platinum–etoposide in advanced large-cell neuroendocrine lung carcinoma (aLCNEC)

  • 期刊论文

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  • 发表日期：

    2026年6月23日

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  • Elizabeth Dudnik,
  • Hovav Nechushtan,
  • Ofer Rotem,
  • Ekaterina Hanovich,
  • Mira Wollner,
  • Tatiana Boikaner,
  • Niel Fridman,
  • Jonathan Ofer,
  • Merav A. Ben-David,
  • Daniel Reinhorn

摘要

Background

LCNEC is a rare high-grade neuroendocrine malignancy with poor prognosis and limited evidence to guide systemic therapy.

Methods

Prospective, single-arm phase II study of 1st-line durvalumab 1500 mg + cisplatin or carboplatin and etoposide (EP) q3 weeks for 4 cycles, followed by durvalumab 1500 mg q4 weeks, in aLCNEC. The primary endpoint was 12-month PFS (RECIST v1.1, radiologist-assessed); secondary endpoints were ORR, OS, and safety. Sample size followed a single-stage Fleming design (one-sided α = 0.10, power 80%) testing a 12-month PFS rate ≤ 5% (H0) vs ≥ 18% (H1). The study closed early due to slow accrual after twelve of twenty-two planned patients were enrolled.

Results

Twelve patients were treated (median age 68y; 66.7% male; 91.7% smokers; 91.7% stage IVB). After median follow-up of 12.8 months (95% CI 8.5–21.3), 92% had progressed and 75% had died. Median PFS was 4.4 months (95% CI 3.1–12.9); 12-month PFS was 25.0% (95% CI 6.0–50.5), exceeding the ≤ 5% null hypothesis (H0) and compatible with the ≥ 18% target (H1). Median OS was 12.8 months (95% CI 5.2–NR); 12-month OS was 58.3% (95% CI 27.0–80.1). ORR was 50.0%, and DCR was 91.7%. All three patients with untreated brain metastases achieved complete intracranial response. Toxicities were mainly grade 1–2; 41.7% had grade 3 adverse events; three discontinued durvalumab for immune-related toxicity; and no treatment-related deaths occurred.

Conclusions

This first prospective evaluation of durvalumab + EP in aLCNEC, though underpowered, demonstrates efficacy and safety consistent with design expectations.