New report from OCDE (FDA’s Oncology Drug Advisory Meeting) considered the use of bevacizumab in first line therapy combined with chemotherapy “not clinically relevant”.
That’s all! Unfortunately for our patients, we all expect good and valuable new treatments; but new drugs must be extensively researched for the benefit of our patients, not drug companies.
What provokes me is that these studies (E2100, AVADO and RIBBON1) were extensively explored by the drug manufacturer worldwide, as well as it's colon cancer twin study (E3200). For me, these practices sounds creepy … a good study stands by itself.
So on…
In july 22nd the FDA advisory committee voted 12 / 1 against bevacizumab use in first line metastatic breast cancer, a knockdown against poor science and poor medicine. See how at the OCDE Report pages 25 and 26 (and 8 below):
“IV. SUMMARY
The addition of bevacizumab to docetaxel (AVADO study) and to taxane/anthracyclinebased chemotherapy or to capecitabine (RIBBON1 study) met the pre-specific primary endpoint, with a statistically significant improvement in PFS, however the magnitude of the PFS improvement is not clinically meaningful. The combination of bevacizumab to chemotherapy resulted in an overall increased in serious adverse events, grade 3-5 adverse events, and adverse events related to bevacizumab in both studies. Overall survival data showed hazard ratios favoring the placebo arms for AVADO study and RIBBON1 (taxane/anthracycline cohort), indicating an inferior outcome with the addition of bevacizumab to these chemotherapies.
AVADO and RIBBON 1 are well-conducted, double-blinded trials, with less missing data compared to E2100. The improvement in PFS observed in these two studies, as measured by the hazard ratio and as more commonly expressed by clinicians as the difference in median PFS between the treatment arms, failed to confirm the magnitude of PFS improvement observed in the E2100 trial, the basis for the accelerated approval. The magnitude of treatment effect is clinically important because it is really a measure of delaying symptoms from tumor progression, which has to be weighed against drug toxicity that is present for the duration of treatment
The risk-benefit ratio of bevacizumab when added to the standard the chemotherapeutic regimens serving as standard of care in the AVADO and RIBBON1 studies may not be considered favorable. FDA seeks the Committee’s advice on whether clinical benefit has been demonstrated in these applications.”
The addition of bevacizumab to docetaxel (AVADO study) and to taxane/anthracyclinebased chemotherapy or to capecitabine (RIBBON1 study) met the pre-specific primary endpoint, with a statistically significant improvement in PFS, however the magnitude of the PFS improvement is not clinically meaningful. The combination of bevacizumab to chemotherapy resulted in an overall increased in serious adverse events, grade 3-5 adverse events, and adverse events related to bevacizumab in both studies. Overall survival data showed hazard ratios favoring the placebo arms for AVADO study and RIBBON1 (taxane/anthracycline cohort), indicating an inferior outcome with the addition of bevacizumab to these chemotherapies.
AVADO and RIBBON 1 are well-conducted, double-blinded trials, with less missing data compared to E2100. The improvement in PFS observed in these two studies, as measured by the hazard ratio and as more commonly expressed by clinicians as the difference in median PFS between the treatment arms, failed to confirm the magnitude of PFS improvement observed in the E2100 trial, the basis for the accelerated approval. The magnitude of treatment effect is clinically important because it is really a measure of delaying symptoms from tumor progression, which has to be weighed against drug toxicity that is present for the duration of treatment
The risk-benefit ratio of bevacizumab when added to the standard the chemotherapeutic regimens serving as standard of care in the AVADO and RIBBON1 studies may not be considered favorable. FDA seeks the Committee’s advice on whether clinical benefit has been demonstrated in these applications.”
Going even deeper on report, we will find some really bad science reported, pasted from page 8:
“The review team did not have confidence in the PFS results because baseline or PFS-determining radiographic scans were missing in 10% of the patients and 34% of the patients were not followed until an IRRC-determined PFS event or the end of the study. In addition, there was a high rate of discordance (50%) between investigator and independent review determined PFS events”.
Ops,
34% of the patients were not followed until an
IRRC-determined PFS event or the end of the study?
IRRC-determined PFS event or the end of the study?
50% discordance between investigator and
independent review determined PFS events?
independent review determined PFS events?
If it is not bad science, I don’t know what it is…
…
Slides presented in PDF format: http://ht.ly/2fntf
Report in PDF format: http://ht.ly/2fQ7X
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