The second paper that I’m going to discuss this afternoon was an important study that was led by the MITO-MaNGO Italian cooperative groups in gynaecological cancer as part of the ENGOT collaboration. That was addressing a very important question and that is rechallenging patients with bevacizumab. So in this randomised trial patients who had all received bevacizumab in the frontline setting were randomised at recurrence, at a platinum sensitive recurrence, to either standard second line chemotherapy or that chemotherapy plus the addition of bevacizumab. What the data showed was that by reintroducing bevacizumab into these patients you increase the response rate, which we know is important in patients with recurrent ovarian cancer, and indeed the progression free survival. So it did not appear that resistance to the effect of bevacizumab had developed merely by using that drug in the first line setting.

Interestingly, there were a proportion of patients who, although they had a more than six month interval between the last platinum and relapse, were still on bevacizumab at the time that the disease progressed. These patients were also treated in the trial and the subgroup analysis on the forest plot didn’t show that there was any less effect in these patients either.

So, to me, the interpretation of these data is that tumours don’t become resistant to bevacizumab. There are other factors that cause the tumour to grow through but if you reintroduce the bevacizumab, either with chemotherapy and then as maintenance, you can again extend the benefit in terms of progression free survival. Now, the implications of this are quite important. Partly, in the USA bevacizumab after seven years has now been licensed in the first line setting so more patients in the USA will be receiving the drug first line and the question is can we use it again. In continental Europe it’s licensed in both first line and in second line setting so that gives confidence to clinicians to use the drug again. In the UK we’re in the unfortunate position of not having access to bevacizumab either in the platinum sensitive recurrence setting or, indeed, in the platinum resistant setting. There is an interesting question that people will want to ask themselves is because the PINATA trial has shown bevacizumab after bevacizumab in the platinum sensitive setting is beneficial. Can we assume, infer, that we can use the drug in the platinum resistant setting again, having used it in the first line setting? When the original data came out on the AURELIA trial for platinum resistant disease it was in patients who had not previously received bevacizumab. So people will be asking that question and I don’t think anyone is going to be doing a trial of bevacizumab after bevacizumab in that setting but people will make that logical step and say if it works in the platinum sensitive setting on rechallenge, why not use it in the platinum recurrent setting? Whether or not the company will be able to get an extension of their label or a change in the label to accommodate that, I don’t know, but in terms of clinicians out there who have the ability to use bevacizumab at different phases of the treatment will probably make that step and that will be entirely reasonable.