ASCO 2012, Chicago, USA
Increased progression-free survival in advanced lung cancer with afatinib
Dr James Yang – National Taiwan University Hospital, Taipei, Taiwan
You’ve been looking at afatinib, now this is a new kind of TKI, looking at it in the setting of non-small cell lung cancer. What were you trying to do here?
This is the first irreversible EGFR inhibitor that is tested in a phase III randomised study. In this study we have shown that, compared with chemotherapy, the progression free survival time was longer and the lung cancer related symptoms were improved as well as quality of life was better.
Now we have, of course, got EGFR TKIs – erlotinib, gefitinib and so on, so how is afatinib different?
In the animal model in the in vitro system this drug can inhibit all four pan-HER family, that is EGFR, HER2, HER3, HER4, and it is an irreversible binding meaning that the inhibition is stronger. Thirdly, in the in vitro system it inhibits the resistant mutation T790M.
And what were your results, then, in terms of tumour response and the overall response rate?
The patients who received afatinib had the overall response rate of 56% versus only 22.6% in patients who received combination chemotherapy.
There was an interesting difference, depending on whether so-called common mutations on exon 19 and exon 21 were present. Could you tell me all about that?
There are several types of EGFR mutations we can detect in lung cancer patients, among them 90% of them belong to one of these two types of mutation, deletion 19 and L858R mutations, they consist of 90% of EGFR mutations. These are more sensitive to EGFR TKIs.
So what are the overall conclusions of your study?
The overall conclusion of our study is afatinib met its endpoint by showing better progression free survival time compared with combination chemotherapy. The PFS was 11.1 months for afatinib and 6.9 months for combination chemotherapy. The hazard ratio is 0.58, highly statistically significant. For patients with common mutations the afatinib had a progression free survival time of 13.6 months versus chemotherapy at 6.9 months. So this is a very big difference.
Now this is, of course, in EGFR positive patients, we’ve been hearing here at the ASCO meeting about the importance of molecular testing, how much difference could this make and what do you now advise doctors to be doing with their patients?
In patients who had a diagnosis with lung adenocarcinoma they should do the molecular testing to see whether they have this type of mutation, EGFR mutations. If they do have this mutation I would urge them to select one of the EGFR TKIs as a first line treatment.