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

Masato Karayama; Takafumi Suda; Kiyotaka Yoh; Kazuhiro Usui; Yukio Hosomi; Kazuma Kishi; Go Naka; Kageaki Watanabe; Shu Tamano; Kohei Uemura; Hideo Kunitoh

doi:10.1016/j.lungcan.2024.108037

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 Nov 26:198:108037. doi: 10.1016/j.lungcan.2024.108037. Online ahead of print.

Authors

Masato Karayama¹, Takafumi Suda², Kiyotaka Yoh³, Kazuhiro Usui⁴, Yukio Hosomi⁵, Kazuma Kishi⁶, Go Naka⁷, Kageaki Watanabe⁵, Shu Tamano⁸, Kohei Uemura⁹, Hideo Kunitoh¹⁰

Affiliations

¹ Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. Electronic address: karayama@hama-med.ac.jp.
² Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
³ Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan.
⁴ Department of Respiratory Medicine, NTT Medical Center Tokyo, Shinagawa, Tokyo 141-0022, Japan.
⁵ Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo, Tokyo 113-8677, Japan.
⁶ Department of Respiratory Medicine, Toho University Omori Medical Center, Ota, Tokyo 143-8541, Japan.
⁷ Department of Respiratory Medicine, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan; Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo 30-1, Japan.
⁸ Biostatistics and Bioinformatics Course, Graduate School of Interdisciplinary Information Studies, The University of Tokyo, Bunkyo, Tokyo 113-8655, Japan.
⁹ Department of Biostatistics and Bioinformatics, The Interfaculty Initiative in Information Studies, The University of Tokyo, Bunkyo, Tokyo 113-8655, Japan.
¹⁰ Department of Chemotherapy, Japan Red Cross Medical Center, Shibuya, Tokyo 150-8935, Japan.

PMID: 39602849
DOI: 10.1016/j.lungcan.2024.108037

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.