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Christine MH-UK · 01-11-2006, 04:05 AM

OK, I'm a cheapskate. Instead of spending the money, I have tried to figure out what it probably said and rebut it because I can tell everyone is getting upset. Did I get it right?

" The crucial difference between 'relative risk' and 'absolute risk' and how that difference has been used to exaggerate the importance of the Herceptin findings." Doesn't this just mean that herceptin reducing recurrence by 50% only means that recurrence is halved, not that somebody with a 50% chance of it coming back without herceptin gets a guaranteed cure with it (50%+50% being 100%), which we already know. Still, somebody with a 50% of disease free survival would surely welcome improving that to a 75% chance of disease free survival.

" The difference between disease-free survival and overall survival and why a focus on 'disease-free survival' can obscure the weak performance of a treatment." I guess he means that improved disease free survival doesn't prove that the drug isn't just delaying the onset of the secondary disease and improving overall survival. This is a major question, but the problem here, of course is that herceptin for secondary patients has greatly improved survival after recurrence, so any difference takes a while to show up. This point is legitimate, though.

"What did these studies really show about overall survival, and in particular what is surprisingly revealed in one of the charts on survival?" I think he means here that there is a chart that shows that patients who recur when receiving early herceptin live no longer than those who never received it in the first place. Which isn't that surprising, since those patients clearly have a herceptin resistant cancer. Maybe he also means that herceptin doesn't do a thing against CNS and brain mets (and don't we all know that one?). Still, there are all those patients who don't recur.

"What life-threatening complication is seen so often that it reduces the actual benefit of Herceptin to almost nothing?" He must be talking about cardiotoxicity here, but this varies between the trials from none (HERA, FinHer) to very low (HCT) to very high (the ones using adriamycin). Risks and benefits would also really depend on a particular patient's relative risks of heart disease versus death from cancer.

"Which other standard drugs—already received by a majority of breast cancer patients—increase the potentially fatal adverse effects of Herceptin?" Anthracyclines, which is why Slamon recommended HCT in his SABCS talk. Interestingly, if you look at the charts from that talk, the main culprit in cardiotoxicity is the conventional treatment, since cardiotoxicity shows up in the AC->taxotere control arm as well. HCT produced 30% fewer recurrences than AC->taxotere with much LOWER cardiotoxicity.

"Why patients over 50 years of age are harmed more and benefited less by Herceptin? Why patients in community clinics are unlikely to benefit as much as those in clinical trials?" Older patients are more likely to suffer heart problems. Benefitted less, though? I am not sure that you can say this. The only data are from HERA and it had relatively few patients over 60, which makes it difficult to judge the relative benefit, since the trial wasn't set up for this. I would guess that the monitoring in community clinics may not be as good as those on trials.

"Why did doctors stop this clinical trial early, before the full effects of Herceptin and other treatments had a chance to fully play themselves out?" This one I don't know. I know that HERA had planned to announce in San Antonio and had to declare early because of the US trials had decided to announce early. Maybe the scientists wanted to be first and get all the glory.
What does Moss suggest?

"What are some of the other drawbacks of Herceptin? Why does this 'targeted' drug, touted as a nontoxic miracle, routinely cause serious adverse effects in over 40 percent of patients?" OK, finally one that has me stumped and I have read just about everything on side effects.

"Which of the researchers currently promoting Herceptin as a cure for breast cancer are financially entangled with the manufacturers of this drug?" It depends on what you mean by 'entangled.' All of the trials, except I believe Finher, received some funding from Roche or Genentech. According to the Finher listing on an oncology website, it only received Finnish money and funding from Sanofi-Aventis. Like the Roche and Genentech funded trials, it indicates that herceptin does work against breast cancer and, indeed, that it may work so well that much less of it is needed.

"Which famous medical journal has also criticized the hyping of Herceptin?" The Lancet editorial, which I posted in the articles of interest section. The main valid criticism is that putting the results of the two US trials together raises questions about whether overall survival has been improved. The Finher trial, which had no financial stake, is nonetheless pretty close to achieving statistically significant overall survival and will help to resolve this issue I hope.

Personally I think that the worst one can say is that the only big trial with no heart problems reduced recurrence over AC->taxotere alone by a statistically significant 30%, that improved overall survival has not been decisively demonstrated, and that the big trials probably used excessive amounts of herceptin.

Okay, how did I do? Did I guess right?

01-11-2006, 04:05 AM	#15
Christine MH-UK Senior Member Join Date: Sep 2005 Posts: 414	But we already know the answers to lots of this OK, I'm a cheapskate. Instead of spending the money, I have tried to figure out what it probably said and rebut it because I can tell everyone is getting upset. Did I get it right? " The crucial difference between 'relative risk' and 'absolute risk' and how that difference has been used to exaggerate the importance of the Herceptin findings." Doesn't this just mean that herceptin reducing recurrence by 50% only means that recurrence is halved, not that somebody with a 50% chance of it coming back without herceptin gets a guaranteed cure with it (50%+50% being 100%), which we already know. Still, somebody with a 50% of disease free survival would surely welcome improving that to a 75% chance of disease free survival. " The difference between disease-free survival and overall survival and why a focus on 'disease-free survival' can obscure the weak performance of a treatment." I guess he means that improved disease free survival doesn't prove that the drug isn't just delaying the onset of the secondary disease and improving overall survival. This is a major question, but the problem here, of course is that herceptin for secondary patients has greatly improved survival after recurrence, so any difference takes a while to show up. This point is legitimate, though. "What did these studies really show about overall survival, and in particular what is surprisingly revealed in one of the charts on survival?" I think he means here that there is a chart that shows that patients who recur when receiving early herceptin live no longer than those who never received it in the first place. Which isn't that surprising, since those patients clearly have a herceptin resistant cancer. Maybe he also means that herceptin doesn't do a thing against CNS and brain mets (and don't we all know that one?). Still, there are all those patients who don't recur. "What life-threatening complication is seen so often that it reduces the actual benefit of Herceptin to almost nothing?" He must be talking about cardiotoxicity here, but this varies between the trials from none (HERA, FinHer) to very low (HCT) to very high (the ones using adriamycin). Risks and benefits would also really depend on a particular patient's relative risks of heart disease versus death from cancer. "Which other standard drugs—already received by a majority of breast cancer patients—increase the potentially fatal adverse effects of Herceptin?" Anthracyclines, which is why Slamon recommended HCT in his SABCS talk. Interestingly, if you look at the charts from that talk, the main culprit in cardiotoxicity is the conventional treatment, since cardiotoxicity shows up in the AC->taxotere control arm as well. HCT produced 30% fewer recurrences than AC->taxotere with much LOWER cardiotoxicity. "Why patients over 50 years of age are harmed more and benefited less by Herceptin? Why patients in community clinics are unlikely to benefit as much as those in clinical trials?" Older patients are more likely to suffer heart problems. Benefitted less, though? I am not sure that you can say this. The only data are from HERA and it had relatively few patients over 60, which makes it difficult to judge the relative benefit, since the trial wasn't set up for this. I would guess that the monitoring in community clinics may not be as good as those on trials. "Why did doctors stop this clinical trial early, before the full effects of Herceptin and other treatments had a chance to fully play themselves out?" This one I don't know. I know that HERA had planned to announce in San Antonio and had to declare early because of the US trials had decided to announce early. Maybe the scientists wanted to be first and get all the glory. What does Moss suggest? "What are some of the other drawbacks of Herceptin? Why does this 'targeted' drug, touted as a nontoxic miracle, routinely cause serious adverse effects in over 40 percent of patients?" OK, finally one that has me stumped and I have read just about everything on side effects. "Which of the researchers currently promoting Herceptin as a cure for breast cancer are financially entangled with the manufacturers of this drug?" It depends on what you mean by 'entangled.' All of the trials, except I believe Finher, received some funding from Roche or Genentech. According to the Finher listing on an oncology website, it only received Finnish money and funding from Sanofi-Aventis. Like the Roche and Genentech funded trials, it indicates that herceptin does work against breast cancer and, indeed, that it may work so well that much less of it is needed. "Which famous medical journal has also criticized the hyping of Herceptin?" The Lancet editorial, which I posted in the articles of interest section. The main valid criticism is that putting the results of the two US trials together raises questions about whether overall survival has been improved. The Finher trial, which had no financial stake, is nonetheless pretty close to achieving statistically significant overall survival and will help to resolve this issue I hope. Personally I think that the worst one can say is that the only big trial with no heart problems reduced recurrence over AC->taxotere alone by a statistically significant 30%, that improved overall survival has not been decisively demonstrated, and that the big trials probably used excessive amounts of herceptin. Okay, how did I do? Did I guess right?