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Pilot Study of Dacomitinib for Patients With Metastatic -Mutant Lung Cancers With Disease Progression After Initial Treatment With Osimertinib. | LitMetric

AI Article Synopsis

  • * In a phase II study, 12 patients who advanced after osimertinib were given dacomitinib to assess its effectiveness, focusing on the objective response rate.
  • * The results showed a low objective response rate of 17%, with a median progression-free survival of 1.8 months, indicating that dacomitinib offers limited benefits for these patients post-osimertinib.

Article Abstract

Unlabelled: Patients with mutant lung cancer have no approved targeted therapies after disease progression on first-line osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Preclinical studies suggest that tumors with both -sensitizing alteration and acquired second-site EGFR resistance alterations after treatment with osimertinib retain sensitivity to second-generation EGFR TKIs. We hypothesized that dacomitinib, a pan-human epidermal growth factor receptor TKI, may be effective in this setting.

Methods: In this phase II study, patients who had progressed on first-line osimertinib were treated with dacomitinib 45 mg orally daily until disease progression or intolerability. The primary end point was objective response rate.

Results: We enrolled 12 patients. Two partial responses were documented (17% objective response rate; 95% CI, 5 to 45). The median progression-free survival was 1.8 months (95% CI, 1.6 to not reached). One patient with an original sensitizing EGFR G719A mutation and one patient without molecular testing available had partial responses, whereas 0 of the 3 patients with second-site acquired resistance mutations (two C797S and one G724S) met the response criteria. The patient with EGFR G719A has an ongoing response at 17 months, which exceeds prior time on osimertinib (11 months).

Conclusion: In the first trial evaluating a second-generation EGFR TKI after first-line third-generation osimertinib, we found that dacomitinib after disease progression on osimertinib has limited benefit.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232442PMC
http://dx.doi.org/10.1200/PO.21.00005DOI Listing

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