Jan 11th, 2018. Yesterday, a report about a targeted agent against lung cancer was published in the New England Journal of Medicine, which is the most powerful and famous medical journal in the world.
Drugs inhibiting receptors of epidermal growth factor (medically, we call it as 'epdermal growth factor receptor tyrosin kinase inhibitor, EGFR-TKI') is widely used to treat various cancers. Mutations of EGFR is often found in non-small cell lung cancer, so that the drugs targeting EGFR is commonly used for patients with lung cancer.
Osimertinib, which is introduced in this report, is a 3rd generation targeted agent against EGFR. The characteristics of Osimertinib are as in the followings:
- to be administered orally.
- irreversibly bind to EGFR and never fall apart.
- selectively inhibits mutated EGFR, not to wild-type EGFR.
There have been expectations that it will be more effective and less toxic due to those charcteristics above. However, there are lack of clinical evidences, so for now, it is used in patients with metastatic non-small cell lung cancer who have disease progression after other EGFR-TKI therapy.
However, the study above elucidated effectiveness of Osmiertinib as first-line therapy for patients with advanced non-small cell lung cancer.
In other words, this study confirms whether Osmiertinib can be used in patients who are first diagnosed as metastatic lung cancer and start treatment.
The subjects were randomly assigned in 1:1 ratio to receive either osimertinib or a standard EGFR targeted agent (gefitinib or erlotinib).
Osimertinib has significantly increased survival compared to conventional therapy. Two survival end points were used in this study: the progression-free survival (PFS), which is defined as the period during which the disease has not progressed and has stabilized or diminished, and the overal survival.
The median progression-free survival was significantly longer with osimertinib that with conventional therapy (18.9 months vs. 10.2 months). Data on overall survival were immature in this report.
Serious adverse events of grade 3 (medical intervention required and hospitalisation possible) or higher were less frequent with Osimertinib than with conventional therapy.
Which patients will be applied in the future?
It is a study publised just yesterday, so we need to see when it is registered as standard therapy and will be applied to real clinic. I think that Osimertinib therapy can be applied in patients with EGFR-positive stage IV non-small cell lung cancer. In addition, since it has fewer side effects and oral administration is possible, I expect that clinical trials investigating Osimertinib therapy in patients with stage II-III lung cancer can be carried out in the future as well.
- J.-C. Soria, Y. Ohe, J. Vansteenkiste, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer. NEJM, 2018:378(2)113-125.