3児の親さん薬剤師のブログ

とある薬剤師です。感染症治療を考える素材をちょこっと提供。noteもあります https://note.com/twin1980

A Higher Proportion of the EGFR T790M Mutation May Contribute to the Better Survival of Patients with Exon 19 Deletions Compared with Those with L858R.

Journal Club

プレゼンターは、呼吸器内科医です。

2017年 に発表された、肺がんにおけるT790M変異と生存の関係性を確認した報告。


Abstract

 

INTRODUCTION:

 

Increasing evidence has demonstrated that exon 19 deletions (Del19) and L858R mutation in EGFR have different prognostic and predictive roles in NSCLC. We aimed to investigate whether these two mutations produced differences in mechanisms of resistance to EGFR tyrosine kinase inhibitors.

METHODS:

 

Consecutive patients with advanced EGFR-mutant NSCLC who acquired resistance to EGFR tyrosine kinase inhibitors and underwent postprogression biopsy were enrolled. Mechanisms including T790M mutation, mesenchymal-epithelial transition proto-oncogene (MET) amplification, and histological transformation, as well as KRAS, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation, and anaplastic lymphoma receptor tyrosine kinase gene (ALK) fusion, were analyzed.

RESULTS:

 

The prevalence of T790M mutation was significantly higher in the Del19 subgroup than that in L858R subgroup (50.4% versus 36.5%, p = 0.043). Apart from this, there was no difference in other mechanisms including MET amplification and histological transformation. The median overall survival (OS) of patients with T790M mutation was 36.0 months (95% confidence interval [CI]: 30.9-41.2), which was significantly longer than the 26.5 months (95% CI: 24.0-29.0) in MET-positive patients, 19.7 months (95% CI: 18.2-21.2) in patients with histological transformation, and 23.0 months (95% CI: 17.4-28.6) in the KRAS/PIK3CA/ALK-altered population (p = 0.021). The hazard ratios of the MET-amplification subgroup and subgroup with histological transformation were 1.809-fold and 2.370-fold higher than that in T790M-positive subgroup. The median OS times were months 33.3 (95% CI: 28.9-37.7) in the Del19 subgroup and 26.4 months (95% CI: 23.2-29.6) in the L858R subgroup (p = 0.028). However, in multivariable analysis adjusted for T790M genotype, the EGFR mutation subtype was no longer found to be significant.

CONCLUSIONS:

 

Significant OS benefit was observed in patients with T790M mutation, suggesting that a larger proportion of T790M mutation might contribute to the better survival of patients with Del19.

 

まとめ・感想

 

T790M変異を獲得した患者はその他の耐性メカニズムと比較し予後がよかった。

T790M以外の変異においては予後に差がなかった。

Del19はT790Mを獲得する割合が多いため、Del19は予後が期待できうる。

 

今回は、薬学実習生と研修医も参加したが、私も含め変異の基礎知識が少なく、批判的吟味や有意義な議論ができなかった。

とても面白い分野なので、基礎から見直していきたい。