Science and Research

Small cell transformation in EGFR-mutated non-small cell lung cancer: DLL3 expression and efficacy of immune checkpoint inhibitors or tyrosine kinase inhibitors combined with chemotherapy

INTRODUCTION: Small cell transformation (SCT) is a typical mechanism of adaptive resistance to third generation epidermal growth factor receptor inhibitors (EGFRi) which have become the standard of care for EGFR-driven non-small cell lung cancer (EGFR+ NSCLC). Little is known about the optimal management of SCT patients. This study aimed to compare outcomes under platinum/etoposide chemotherapy alone (chemo) or in combination with EGFR inhibitors (EGFRi+chemo) or immune checkpoint inhibitors (ICI+chemo). In addition, DLL3 expression was explored as potential novel therapeutic target. METHODS: We conducted a retrospective study on patients with EGFR+ NSCLC and SCT treated at 19 centers in Europe and the United States. A total of 47 patients were included of whom 17 received chemo, 20 ICI+chemo, and 10 EGFRi+chemo. We analyzed DLL3 expression by immunohistochemistry. RESULTS: In the entire cohort, median overall survival (OS) from start of first SCT therapy was 11 months (95 % confidence interval [95 %CI] 9.1-12.9) and median progression-free survival (PFS) was 5 months (95 %CI 4.2-5.8). Median PFS was similar in all three groups (chemo and ICI+chemo 4 months, EGFRi+chemo 6 months), and 12-months PFS was 12 % (95 %CI 2 %-31 %), 13 % (95 %CI 0 %-43 %), and 0 % for ICI+chemo, EGFRi+chemo, and chemo, respectively. Median OS in the ICI+chemo group was 13 months (95 %CI 5.5-20.5) compared to 10 months (95 %CI 7.6-12.4) with chemo and EGFRi+chemo (95 %CI 8.1-11.9), respectively. Before and after SCT, 0 % and 93 % of tumors were DLL3-positive. CONCLUSIONS: Our results suggest that ICI+chemo and DLL3-targeting agents are worth further exploration in EGFR+ NSCLC undergoing SCT. PRESENTED ELSEWHERE: Part of this work has been presented at ESMO annual meeting in Madrid, Spain in October 2023 (Poster 1336 P).

  • Saalfeld, F. C.
  • Möller, J.
  • Christopoulos, P.
  • Wenzel, C.
  • Rasokat, A.
  • Wang, X. A.
  • Vathiotis, I.
  • König, D.
  • Illini, O.
  • Grohé, C.
  • Wiesweg, M.
  • Wesseler, C.
  • Schubart, C.
  • Pelusi, N.
  • Rohde, G.
  • Overbeck, T. R.
  • Kirfel, J.
  • Alt, J.
  • Kauffmann-Guerrero, D.
  • Griesinger, F.
  • Kulhavy, J.
  • Allgäuer, M.
  • Klimova, A.
  • Schütz, M.
  • Aust, D. E.
  • Hochmair, M. J.
  • Rothschild, S. I.
  • Syrigos, K. N.
  • Veluswamy, R.
  • Michels, S.
  • Stenzinger, A.
  • Jöhrens, K.
  • Wermke, M.

Keywords

  • Dll3
  • EGFR mutation
  • Immune checkpoint inhibitor
  • Non-small cell lung cancer
  • Small cell transformation
Publication details
DOI: 10.1016/j.ejca.2024.115065
Journal: Eur J Cancer
Pages: 115065 
Work Type: Original
Location: Assoziierter Partner, CPC-M, TLRC
Disease Area: LC
Partner / Member: KUM, Thorax, UKSH (Lübeck)
Access-Number: 39423775

DZL Engagements

chevron-down