Efficacy in patients with EGFR-positive non-small-cell lung cancer treated with dacomitinib who had skin adverse events: post hoc analyses from ARCHER 1050

Future Oncol. 2024;20(37):2971-2982. doi: 10.1080/14796694.2024.2404762. Epub 2024 Oct 3.

Abstract

Aim: We investigated association between skin adverse events (AEs) and efficacy with dacomitinib in patients with EGFR-positive non-small-cell lung cancer (NSCLC).Methods: Post hoc analyses from ARCHER 1050 evaluated efficacy in patients who did and did not experience grade ≥2 skin AEs with dacomitinib. Landmark analyses were performed at 3 and 6 months.Results: In patients who had skin AEs (72.2%) vs. those who did not (27.7%), median progression-free survival was 16.0 vs. 9.2 months, median overall survival (OS) was 37.7 vs. 21.6 months, and objective response rate was 80.2 vs. 61.5%; OS was improved at 3 and 6 months landmark analyses.Conclusion: Presence of grade ≥2 skin AEs was associated with numerically improved efficacy and represents a valuable biomarker of treatment outcome with dacomitinib in patients with advanced NSCLC.Clinical Trial Registration: NCT01774721 (ClinicalTrials.gov).

Keywords: ARCHER 1050; biomarker; dacomitinib; non-small-cell lung cancer; skin disorders.

Plain language summary

The ARCHER 1050 study assessed how the drugs called dacomitinib and gefitinib affected people with non-small-cell lung cancer (NSCLC) who had mutations in the EGFR gene. In this study, people who were treated with dacomitinib lived longer without their cancer getting worse than people who were treated with gefitinib. Skin adverse reactions were higher in people who were treated with dacomitinib than gefitinib. In this follow-up analysis, researchers wanted to see if the treatment effect of dacomitinib was different between people who had skin adverse reactions and people who did not have skin adverse reactions after treatment with dacomitinib. The results from this analysis showed that after treatment with dacomitinib, half of the people who had skin adverse reactions lived for 16.0 months, and half of the people who did not have skin adverse reactions lived for 9.2 months without their cancer getting worse. This study also showed that half of the people who had skin adverse reactions lived for 37.7 months, and half of the people who did not have skin adverse reactions lived for 21.6 months. In summary, the results from this study showed that the treatment effect of dacomitinib was better in people who had skin adverse reactions after treatment with dacomitinib. Therefore, skin adverse reactions can be a marker of better treatment effect in people with NSCLC who had mutations in the EGFR gene when treated with dacomitinib.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • 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* / antagonists & inhibitors
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mutation
  • Progression-Free Survival
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolinones* / administration & dosage
  • Quinazolinones* / adverse effects
  • Quinazolinones* / therapeutic use
  • Treatment Outcome

Substances

  • dacomitinib
  • Quinazolinones
  • ErbB Receptors
  • EGFR protein, human
  • Protein Kinase Inhibitors
  • Antineoplastic Agents

Associated data

  • ClinicalTrials.gov/NCT01774721