AI Article Synopsis

  • - This phase II study tests whether alternating the cancer drugs osimertinib and gefitinib can slow down resistance development in advanced non-small cell lung cancer with the EGFR T790M mutation in 47 patients.
  • - The primary goal was to measure progression-free survival (PFS) at 12 months, but the results showed a PFS rate of only 38%, which didn't meet expectations.
  • - Despite some improvement in specific genetic markers associated with treatment resistance, the study indicates that managing resistance in cancer treatments is complex and involves more factors than just targeting known mutations.

Article Abstract

In this phase II, single arm trial (ACTRN12617000720314), we investigate if alternating osimertinib and gefitinib would delay the development of resistance to osimertinib in advanced, non-small cell lung cancer (NSCLC) with the epidermal growth factor receptor (EGFR) T790M mutation (n = 47) by modulating selective pressure on resistant clones. The primary endpoint is progression free-survival (PFS) rate at 12 months, and secondary endpoints include: feasibility of alternating therapy, overall response rate (ORR), overall survival (OS), and safety. The 12-month PFS rate is 38% (95% CI 27.5-55), not meeting the pre-specified primary endpoint. Serial circulating tumor DNA (ctDNA) analysis reveals decrease and clearance of the original activating EGFR and EGFR-T790M mutations which are prognostic of clinical outcomes. In 73% of participants, loss of T790M ctDNA is observed at progression and no participants have evidence of the EGFR C797S resistance mutation following the alternating regimen. These findings highlight the challenges of treatment strategies designed to modulate clonal evolution and the clinical importance of resistance mechanisms beyond suppression of selected genetic mutations in driving therapeutic escape to highly potent targeted therapies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902357PMC
http://dx.doi.org/10.1038/s41467-024-46008-1DOI Listing

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