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Updated: May 29, 2026

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

Osimertinib plus selumetinib in patients with EGFR-mutated advanced NSCLC with BRAF alterations post-progression on

Zofia Piotrowska1, Sarah B Goldberg2, Jonathan W Goldman3

  • 1Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

European Journal of Cancer (Oxford, England : 1990)
|May 27, 2026
PubMed
Abstract

Insights

The combination of osimertinib and selumetinib showed limited efficacy in patients with advanced non-small cell lung cancer (NSCLC) with BRAF alterations after progressing on osimertinib. The safety profile was as expected, but the combination is not recommended for further study.

Area of Science:

  • Oncology
  • Pharmacology
  • Biomarker Research

Background:

  • The ORCHARD study investigated resistance mechanisms in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after first-line osimertinib treatment.
  • This module focused on the efficacy and safety of combining osimertinib with selumetinib in patients with BRAF alterations.

Purpose of the Study:

  • To evaluate the efficacy and safety of osimertinib plus selumetinib in patients with EGFR-mutated advanced NSCLC and BRAF alterations.
  • To characterize resistance mechanisms and assess novel drug combinations in this patient population.

Main Methods:

  • A phase II platform study involving 16 patients with BRAF fusions or BRAF V600E mutations.
  • Patients received daily osimertinib and twice-daily selumetinib until disease progression or toxicity.
  • Primary endpoint was investigator-assessed objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and overall survival (OS).

Main Results:

  • The objective response rate (ORR) was 7%, with one partial response observed.
  • Median progression-free survival (PFS) was 3.4 months, and median overall survival (OS) was 14.0 months.
  • Grade 3 or higher adverse events occurred in 69% of patients, with diarrhea being the most common (19%).

Conclusions:

  • Osimertinib plus selumetinib demonstrated minimal clinical benefit in EGFR-mutated advanced NSCLC with BRAF alterations post-osimertinib progression.
  • The combination's safety profile was consistent with individual drug profiles, with no new safety signals.
  • The risk-benefit profile does not support further investigation of this combination.
Keywords:
BRAFEGFRNSCLCOsimertinibSelumetinib

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