BREAST CANCER UPDATE 7 of 2006:expert interviews

[heblaj01]

Five expert interviews in this new issue of BREAST CANCER UPDATE, two of which are mostly dedicated to HER2+ cancer (Mark D Pegram ,DebuTripathy)
& two dedicated mostly to ER+ (Victor G Vogel,Robert W Carlson).

Several comments on the usefulness of the OncotypeDx test are also interspersed.

http://www.breastcancerupdate.com/20...rs/default.asp

[Christine MH-UK]

Pegram made a few points that I found interesting in his track on FinHer:
1) All of the herceptin trials had been 'massively overpowered,' i.e. they did not need to be nearly as big as they were.
2) The HERA 2 year arm results are expected out in 2008 (this seems to get perpetually pushed back, which does not seem encouraging). If the 2 year arm proves to be more effective than the 1 year arm, they will not try shorter courses. If the 2 year arm is no better, only then will they try shorter courses. I find it disconcerting that the results announcement date keeps on getting pushed back farther and farther.

[heblaj01]

Christine,
I wonder if the overpowered clinical trial you mention was not a deliberate attempt by the manufacturer of the drug to "clean up" the available pool of available volonteering patients with the aim of depriving a competitor of patients to test its drug. This is apparently a common practice among giant pharmaceutical companies according to revelations from a former high level "insider" of the industry.

[Christine MH-UK]

There are so many her2 positive patients around and lapatinib was not close to entering trials in patients with early breast cancer when this trials finished enrolling patients (2004 or earlier). Maybe Genenetech/Roche figured that the extra time they spent enrolling patients would be easily compensated for by getting to a significant improvement in disease free survival earlier.

I do find it interesting, given the generally overpowered nature of these trials, that on the HERA trial the size of the trial was increased substantially from the original protocol. Back in early 2005 I figured that this increase must indicate that HERA trial would have marginal results. However, since the overall trial was really successful, I wonder whether the trial size was increased in the hopes it would strengthen the case for two years over one year.

I am troubled by the strong incentives that seem to exist for researchers to keep on postponing the announcement about the 2-year arm. The researchers involved undoubtedly want the 2 year arm to have better disease free survival than the 1 year arm. Still, one and a half years after the 1 year arm results were announced at ASCO, we are still in the dark about what has gone on with the 2 yr arm. If the 2-year arm is no better than the 1 year arm then Genentech/Roche stand to lose alot since oncologists seem interested in checking out the results of some small, independent trials, namely Finher and the one in Miami that Hurley did, where the results suggest that herceptin is such a great chemosensitizer that only the 9-12 weeks of herceptin during chemo may be necessary. Now, if the only difference between 9-12 weeks of herceptin-based chemo followed by an anthracycline and anthracycline followed by herceptin-based chemo followed by the rest of the year of herceptin was cost, that wouldn't trouble me, but the FinHer study and the Hurley study seem to indicate that the level of cardiotoxicity is much lower when herceptin is only used with a taxane (+/- carboplatin) and then followed by an anthracycline. I think also that the length of the treatment makes it very difficult for some patients to get back to normal life.

[saleboat]

If I understand the history of the herceptin trials correctly, they were massively overpowered because of advocacy groups, i.e., breast cancer advocacy groups were instrumental in getting as many patients included in the trial as possible. If it weren't for size of the trials, far fewer women would have had access to the drug. There weren't any other competitors to Herceptin at the time for adjuvent therapy, as far as I know.