ESMO 2012

Treatment of ALK+ lung cancer with crizotinib, Profile 1007

Dr Alice Shaw – Massachusetts General Hospital, Boston, USA



Profile 1007 is a large, randomised phase III trial comparing a targeted therapy, crizotinib, with standard chemotherapy for patients with a particular type of lung cancer called ALK+ lung cancer. This type of lung cancer is defined by a genetic abnormality in a gene called ALK, which stands for anaplastic lymphoma kinase, and these patients comprise about 5% of the total population of patients with lung cancer.

What kind of results did you find?

The primary endpoint of this phase III study was progression free survival and we found that the study was very positive in terms of favouring crizotinib. The median progression free survival with crizotinib was 7.7 months as compared to 3 months with chemotherapy, so it more than doubled the progression free survival. In terms of objective response rate we also saw a clear increase in responses with the crizotinib patients, the response rate was 65.3% versus 19.5% with chemotherapy.

How did you choose the patients?

These patients all have a specific type of lung cancer that has a genetic abnormality in a gene called ALK and all patients had their tumours tested in a central laboratory as part of this trial for the presence of the genetic abnormality in ALK. We used a test called fluorescence in situ hybridisation, FISH, which is the standard way to identify patients with this so-called ALK rearrangement.

What about things like toxicity compared to other types of treatment?

In this study crizotinib did have a distinct side effect profile compared to single agent chemotherapy. The side effects that we saw with crizotinib were very similar to what we have reported before in single arm studies of crizotinib. The main side effects were visual disturbance, which tends to be very, very mild; nausea, vomiting, diarrhoea, which of course can be managed appropriately with medicines if needed; some oedema or swelling, primarily peripheral. We did see some transaminitis, so irritation in the liver; in about 16% of our patients they had enough of an elevation in their liver enzymes that we did have to temporarily hold crizotinib, wait for the liver to return to normal and then start the crizotinib at a lower dose. But overall the tolerability of crizotinib was very good and certainly similar to what we see with chemotherapy, if not better.

How should this be impacting the clinic?

I think this data clearly established that crizotinib is superior to standard treatment, which is chemotherapy. In the second line setting it’s single agent chemotherapy, typically with pemetrexed or docetaxel which were the comparators in our study. Now, based on our data, we know for a fact that crizotinib is better in terms of prolonging progression free survival and improving response rate and, I think importantly, we know that crizotinib is better in terms of improving patient symptoms as well as patient quality of life.