Efficacy of atezolizumab, bevacizumab, carboplatin, and paclitaxel for epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer after tyrosine kinase inhibitor failure

Curr Probl Cancer. 2025 Jun:56:101200. doi: 10.1016/j.currproblcancer.2025.101200. Epub 2025 Apr 4.

Abstract

Background: Non-small cell lung cancer (NSCLC) with driver mutations, notably epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase, shows reduced sensitivity to immune checkpoint inhibitors. A subgroup analysis of the IMpower150 data on patients resistant to EGFR tyrosine kinase inhibitors (EGFR-TKI) before enrollment demonstrated prolonged progression-free survival (PFS) with atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) over bevacizumab, carboplatin, and paclitaxel. However, due to the exploratory nature and small sample size, the efficacy of ABCP post-EGFR-TKI failure is still debated. We evaluated ABCP therapy against other platinum-based regimens without immune checkpoint inhibitors in terms of effectiveness and toxicity.

Methods: Data from patients with advanced or recurrent NSCLC harboring EGFR-sensitizing mutations treated with platinum-based chemotherapy or ABCP at five Japanese hospitals were retrospectively analyzed. Propensity score matching compared efficacy outcomes, including overall response rate (ORR), PFS, and OS.

Results: Of 183 EGFR mutation carriers, 33 underwent ABCP therapy, while 150 received platinum-based chemotherapy. Following propensity score matching, 32 and 74 patients were analyzed. In the ABCP group, median PFS and OS were 6.8 and 16.7 months compared to 5.8 and 25.7 months with platinum-based chemotherapy, showing no significant differences in PFS (p = 0.46) and OS (p = 0.85). In liver metastases, ABCP yielded a median PFS of 9.9 versus 6.1 months and an ORR of 62.5 % versus 35.7 % relative to platinum-based chemotherapy, without statistical significance (PFS p = 0.16; ORR p = 0.70).

Conclusion: Compared with platinum-based chemotherapy, ABCP did not improve effectiveness in patients with EGFR-mutated NSCLC after EGFR-TKI failure.

Keywords: Advanced non-small cell lung cancer; Epidermal growth factor receptor mutation; Immunochemotherapy; Immunotherapy; Platinum-based chemotherapy.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / pharmacology
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bevacizumab / pharmacology
  • Bevacizumab / therapeutic use
  • Carboplatin / pharmacology
  • Carboplatin / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / secondary
  • Drug Resistance, Neoplasm
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mutation
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Retrospective Studies
  • Tyrosine Kinase Inhibitors / pharmacology
  • Tyrosine Kinase Inhibitors / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • atezolizumab
  • Bevacizumab
  • Carboplatin
  • EGFR protein, human
  • ErbB Receptors
  • Paclitaxel
  • Tyrosine Kinase Inhibitors