Difference in efficacy of osimertinib between patients with EGFR-positive NSCLC with postoperative recurrence and those with de novo unresectable disease: A prospective, observational study

Lung Cancer. 2024 Dec:198:108037. doi: 10.1016/j.lungcan.2024.108037. Epub 2024 Nov 26.

Abstract

Background: Although clinical trials of systemic chemotherapy for advanced non-small-cell lung cancer (NSCLC) have included both postoperative recurrence and de novo unresectable cases, postoperative recurrence is reported to have a better efficacy and prognosis. However, there are no efficacy data of first-line osimertinib for postoperative recurrence.

Methods: We conducted a post hoc analysis of a multicenter, prospective, observational study that evaluated the efficacy of first-line osimertinib in patients with epidermal growth factor receptor (EGFR)-positive NSCLC. The patients were divided into two groups: those with postoperative recurrence (recurrence group, n = 167) and those with de novo unresectable disease (de novo group, n = 385).

Results: The recurrence group had a significantly better Eastern Cooperative Oncology Group performance status (ECOG-PS, p < 0.001) and fewer bone metastases (p < 0.001), brain metastases (p < 0.001), cancer pleurisy (p = 0.006), pleural dissemination (p = 0.003), liver metastases (p = 0.017), and adrenal metastases (p = 0.009) at the start of osimertinib than the de novo group. The recurrence group had a significantly better progression-free survival (PFS) and overall survival (OS) than the de novo group (hazard ratio [HR] = 0.62, 95 % confidence interval [CI], 0.49-0.81, p < 0.001; and HR = 0.58, 95 % CI, 0.43-0.79, p < 0.001, respectively). In a 1:1 propensity score-matching analysis, the matched recurrence group had significantly better PFS and OS than the matched de novo group (HR = 0.72, 95 % CI, 0.52-0.99, p = 0.034; and HR = 0.65, 95 % CI, 0.44-0.95, p < 0.001, respectively).

Conclusion: Patients with EGFR-positive NSCLC and postoperative recurrence have a better ECOG-PS and fewer distant metastases at the start of first-line osimertinib, and better PFS and OS than those with de novo unresectable disease. Postoperative recurrence should be considered as a stratification factor in future clinical trials for advanced EGFR-positive NSCLC.

Keywords: Adjuvant chemotherapy; Driver gene mutation; Epidermal growth factor receptor; Lung cancer; Relapse; Targeted therapy.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Acrylamides* / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds* / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • ErbB Receptors* / genetics
  • ErbB Receptors* / metabolism
  • Female
  • Humans
  • Indoles
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local*
  • Prognosis
  • Prospective Studies
  • Pyrimidines
  • Treatment Outcome

Substances

  • osimertinib
  • Acrylamides
  • Aniline Compounds
  • ErbB Receptors
  • EGFR protein, human
  • Antineoplastic Agents
  • Indoles
  • Pyrimidines