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Osimertinib in non-small cell lung cancer patients with uncommon EGFR mutation


Approximately 10% of EGFR mutants harbor uncommon mutations, which represent a heterogeneous group of rare molecular alterations within exons 18-21 and the sensitivity to EGFR tyrosine kinase inhibitors ( TKIs ) is variable.

Osimertinib ( Tagrisso ) is a potent irreversible inhibitor of both sensitizing EGFR mutation and T790M.
In preclinical data, the potency of Osimertinib against uncommon EGFR mutants other than exon 20 insertion was fairly good.

The efficacy and safety of Osimertinib in patients with uncommon EGFR mutation positive NSCLC were presented.

Patients with histologically confirmed metastatic or recurrent NSCLC with activating EGFR mutation other than exon 19 deletion, L858R, T790M and insertion in exon 20 were eligible.
Patients received 80mg of Osimertinib per oral daily until progression or unacceptable toxicity. Response was assessed every 8 weeks by investigator.

Between Mar 2016 and Oct 2017, 36 patients were enrolled. Median age was 59.5, 61% male, 44% never smoker, 97% adenocarcinoma. 61% of patients were treated as first-line therapy.
The most common mutations were G719A/C/D/S/X ( 19, 52.8% ) followed by L861Q ( 9, 25% ), S7681 ( 8, 22% ), and others ( 4, 11% ).

The overall response rate ( ORR ) was 50.0% ( 95% CI 32.8-67.2 ) and DCR was 88.9% ( 95% CI 78.1-99.7 ).

Seven patients ( 77.8% ) with L861Q mutation achieved partial response; 10 ( 52.6% ) with G719A/C/D/S/X mutation; three ( 37.5% ) with S768I mutation.

At data cutoff ( Nov, 2017 ), the median progression-free survival ( PFS ) was 9.5 months ( range 1.0-20.1 ) and median duration of response was 7.0 months ( 95% CI 4.7-9.3 ).

The most common adverse events were rash ( n = 11, 30.6% ), anorexia ( n = 8, 22.2% ), and diarrhea ( n = 7, 19.4% ).
Grade 3 or 4 adverse effect were reported in 8 of 36 patients ( 22% ), but all of adverse effects were manageable.

In conclusion, Osimertinib showed highly active and durable in patients with non-small cell lung cancer harboring uncommon EGFR mutation with manageable safety profile, consistent with previous reports. ( Xagena )

Source: American Society of Clinical Oncology - ASCO Meeting, 2018

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