A phase II study of daily carboplatin plus irradiation followed by durvalumab therapy for older adults (≥75 years) with unresectable III non-small-cell lung cancer and performance status of 2: NEJ039A

ESMO Open. 2024 Oct;9(10):103939. doi: 10.1016/j.esmoop.2024.103939. Epub 2024 Oct 11.

Abstract

Background: Standard care for unresectable locally advanced non-small-cell lung cancer (LA-NSCLC) involves chemoradiotherapy followed by durvalumab. The clinical significance of durvalumab after chemoradiotherapy in patients with LA-NSCLC having a performance status of 2 or aged ≥75 years, however, remains unclear. Therefore, we investigated the clinical benefit of durvalumab after daily carboplatin plus thoracic concurrent radiotherapy.

Patients and methods: In this prospective phase II study, daily low-dose carboplatin (30 mg/m2) was administered before radiotherapy for the first 20 fractions and concurrent radiotherapy (60 Gy) followed by durvalumab. The primary endpoint was 12 months progression-free survival (PFS) rate from durvalumab initiation. The secondary endpoints included rate of therapeutic completion, PFS, overall survival, objective response rate, and safety.

Results: Of 86 patients who underwent chemoradiotherapy with daily carboplatin from September 2019 to October 2021, 61 (70.9%) received durvalumab consolidation. The performance status was 0, 1, and 2 in 28 (45.9%), 26 (42.6%), and 7 (11.5%) patients, respectively. The rate of therapeutic completion for durvalumab was 26.2% (16/61). The PFS rate of 12 months after durvalumab initiation was 51.0%, indicating that the primary endpoint was achieved because the expected value of 35% calculated from previous studies was exceeded. The objective response rate after chemoradiotherapy and durvalumab was 47.0% and 57.4%, respectively. The median PFS and overall survival were 12.3 and 28.1 months, respectively. The most common adverse event in grades 3 or 4 was pneumonitis (8.2%). One patient died because of interstitial pneumonitis.

Conclusions: Durvalumab consolidation after daily carboplatin with radiotherapy was effective and tolerable for LA-NSCLC vulnerable patients.

Keywords: durvalumab; locally advanced NSCLC; older adult; performance status 2.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal* / pharmacology
  • Antibodies, Monoclonal* / therapeutic use
  • Carboplatin* / pharmacology
  • Carboplatin* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Chemoradiotherapy* / methods
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / radiotherapy
  • Male
  • Prospective Studies

Substances

  • Carboplatin
  • durvalumab
  • Antibodies, Monoclonal