Advanced NSCLC: EGFR genotype tied to osimertinib outcomes

  • Igawa S & al.
  • Cancer Manag Res
  • 1 Jan 2019

  • curated by Emily Willingham, PhD
  • Univadis Clinical Summaries
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Takeaway

  • Among patients with T790M-positive advanced NSCLC with resistance to first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), the exon 19 deletion EGFR genotype is linked to better outcomes with second-line osimertinib vs the L858R point-mutation genotype.
  • Exon 19 deletion is tied to better response rate and PFS, OS.

Why this matters

  • Genotype-based efficacy differences in advanced TKI-resistant NSCLC have not been previously clarified, say the authors.

Key results

  • 29/51 patients showed an objective response (58.8%; 95% CI, 42.3%-75.3%); however, the rate was: 
    • 69.7% (50.0%-89.4%) with exon 19 deletion, vs
    • 38.9% (18.0%-59.7%) with L858R (P=.033).
  • For the entire group, median PFS was 7.8 (95% CI, 6.7-8.9) months, and median OS was 15.5 (10.0-21.0) months.
  • Median PFS by genotype:
    • 8.0 (6.4-9.6) months with exon 19 deletion, vs
    • 5.2 (3.5-6.9) months with L858R (P=.045). 
  • Median OS by genotype:
    • 19.8 (13.0-26.6) months with exon 19 deletion, vs
    • 12.9 (1.9-23.9) months with L858R (P=.0015).
  • Exon 19 deletion independently predicted favorable PFS, OS. 

Study design

  • Prospective observational cohort study, n=51 (65% female; media age 71 years; 33 with exon 19 deletion) treated with osimertinib, May 2016-October 2018.
  • Funding: None disclosed.

Limitations

  • All Asian population. 
  • Single institution, small cohort.
  • Genotype groups differed in some characteristics.  

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