Real-world outcomes of subsequent treatment strategies after durvalumab consolidation in stage III unresectable non-small cell lung cancer

Lung Cancer. 2025 Jun:204:108576. doi: 10.1016/j.lungcan.2025.108576. Epub 2025 May 3.

Abstract

Background: The PACIFIC trial established chemoradiation followed by 1-year durvalumab consolidation as standard of care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC). This study aims to investigate therapeutic strategies and clinical outcomes after durvalumab failure in the real-world.

Materials and methods: Patients with stage III LA-NSCLC from 23 Italian centres were retrospectively enrolled at durvalumab progression. Subsequent treatments (Sub-Tx) were prospectively collected and classified as follows:chemo-immunotherapy (subgroup-1), platinum-based chemotherapy (subgroup-2), non-platinum-based chemotherapy (subgroup-3), and targeted therapy (subgroup-4). Durvalumab progression free survival (Dur-PFS) and overall survival (Dur-OS), as well as outcomes of Sub-Tx (Sub-PFS and Sub-OS) were estimated by using the Kaplan-Meier approach.

Results: A total of 122 patients were enrolled. Median Dur-PFS was 9.3 months (95 % CI: 7.1 - 11.4) and median Dur-OS 24.2 months (95 % CI: 18.7 - 29.7). Out of 93 patients receiving a Sub-Tx, 21.5 %, 43.0 %, 28.0 %, and 7.5 % were in the subgroup 1, 2, 3, and 4, respectively. Median Sub-PFS were 12.0, 4.1, 2.7, and 6.0 months, respectively. Patients who completed 12 months of durvalumab were 65.0 %, 27.5 %, 19.2 %, and 42.9 % across the four subgroups. In univariate analysis, the duration of durvalumab therapy was an independent factor for selecting Sub-Tx (p < 0.007). Median time to next treatment (TTNT) was 6.7 months with chemo-immunotherapy and 2.1 with chemotherapy (p = 0.009). Out of 15 patients with a TTNT > 1 year, 40 % were rechallenged with immunotherapy.

Conclusion: Platinum-based chemotherapy was the predominant treatment after durvalumab consolidation. Immunotherapy rechallenge was associated with the best survival outcome in selected cases, warranting further investigation.

Keywords: Immunotherapy; Locally advanced; Non-small cell lung cancer; Rechallenge; Stage III; Unresectable.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal* / therapeutic use
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Consolidation Chemotherapy
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / therapy
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Retrospective Studies
  • Treatment Outcome

Substances

  • durvalumab
  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological