J. Clin. Oncol. 2019 Dec 11
Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09).
Abstract
Purpose
Approximately 10% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) harbor uncommon mutations. Here, we report the efficacy and safety of osimertinib in patients with NSCLC harboring uncommon EGFR mutations.
Patient and methods
This was a multicenter, single-arm, open-label, phase II study in Korea. Patients with histologically confirmed metastatic or recurrent NSCLC harboring EGFR mutations other than the exon 19 deletion, L858R and T790M mutations, and exon 20 insertion were eligible for the study. The primary end point of objective response rate was assessed every 6 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary end points were progression-free survival, overall survival, duration of response, and safety.
Results
Between March 2016 and October 2017, 37 patients were enrolled. All were evaluable except one patient who withdrew consent after starting treatment. Median age was 60 years, and 22 (61%) were male. Among patients, 61% received osimertinib as first-line therapy. The mutations identified were G719X (n = 19; 53%), followed by L861Q (n = 9; 25%), S768I (n = 8; 22%), and others (n = 4; 11%). Objective response rate was 50% (18 of 36 patients; 95% CI, 33% to 67%). Median progression-free survival was 8.2 months (95% CI, 5.9 to 10.5 months), and median overall survival was not reached. Median duration of response was 11.2 months (95% CI, 7.7 to 14.7 months). Adverse events of any grade were rash (n = 11; 31%), pruritus (n = 9; 25%), decreased appetite (n = 9; 25%), diarrhea (n = 8; 22%), and dyspnea (n = 8; 22%), but all adverse events were manageable.
Conclusion
Osimertinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations.
Related Questions
Would you add immunotherapy to chemotherapy for a patient with metastatic NSCLC, an atypical EGFR mutation, and PD-L1 ≥50% who has progressed on osimertinib?
This is a difficult scenario, and there is no data to guide this. There is good evidence to suggest that patients with the classical mutations do not respond to ICIs regardless of PD-L1 expression. There is one small retrospective analysis that included 7 patients with uncommon mutations (G719X and ...
Would you consider adjuvant osimertinib for patients with non-classical but sensitizing EGFR mutation positive NSCLC s/p surgical resection?
While uncommon, EGFR mutations were not included in the ADAURA trial (and thus may not be covered by 3rd party insurance), I will consider using osimertinib in the adjuvant setting for high risk patients with certain atypical/uncommon EGFR mutations, i.e. mutations wherein structure-based modeling a...
Are there any subsets of patients where you would consider first-line dacomitinib for EGFR mutations positive NSCLC?
I continue to favor osimertinib as front line therapy for patients with EGFR mutation positive NSCLC. A retrospective analysis of response and benefit of osimertinib in some less common EGFR mutations was published, including G719X, L861Q, and S768I. The analysis showed clinical benefit with osimert...
Would you consider first line osimertinib to patients with an EGFR Exon 18 G719X mutation?
Yes, there is some retrospective data that osi (or afatinib) are reasonable options here