Media accounts and medical progress haters like Merrill Goozner are claiming that the FDA said Avastin in advanced breast cancer is "unsafe."
What the FDA advisory panel (stacked by Richard Padzur, who heads up the Office of Cancer Drugs, with 6 advisors who wanted to yank Avastin last year) said was that based on the FDA's read of the data, Avastin despite causing a doubling in median progression free survival and objective response in tumors as well as an overall medial survival of two additional months in a subgroup of patients who were the most likely to die without Avastin (that's my take) and were more likely to die of cancer should not be used for breast cancer because it caused too much hypertension, bleeding and swelling.
Hal Barron, Executive Vice President, Head of Global Development: Oncology, Inflammation, and Virology at Genentech -- Avastin's creator -- summed up the FDA's (Padzur) deadly decision: The FDA (Padzur) would have allowed the Avastin indication to stay if it was really treating an unmet medical need. In otherwords, the FDA (Padzur) would have not stacked the deck against Avastin if the FDA (Padzur) thought that giving thousands of women longer life and better health.
The FDA switched the endpoints and oncologists, health plans and patients know it even as The Gooz oozes glee over the Avastin decision and derides the additional benefit to thousands of patients as just in their minds. Here's what Padzur said in his summary of evidence against Avastin.
"AVADO showed a statistically significant improvement in PFS for the bevacizumab-containing arms, with a HR of 0.70 (95% CI 0.55, 0.90) for 7.5 mg/kg
bevacizumab arm and HR of 0.62 (95% CI 0.48, 0.79) for the 15 mg/kg bevacizumab arm. The magnitude of treatment effect, as commonly assessed by clinicians based on
differences in median PFS, was marginal."
Genentech had called out this shifting of evidentiary standards in a pre-hearing summary of evidence:
"Although it was clear that AVADO and RIBBON1 (the two studies FDA, I mean Padzur, wanted to confirm the benefit of Avastin) were not powered to show an OS benefit, the agency now cites the studies for failing to show a statistically significant OS effect. Then, CDER stated only after its decision to withdraw Avastin’s MBC indication that any PFS effect “must confirm the magnitude of treatment effect of E2100."
Also: " CDER also has not articulated a clear rationale for its view that a 5.5-month improvement in median PFS is clinically meaningful but lesser improvements are not."
www.gene.com/gene/news/news-events/avastin/documents/051311.pdf
FDA might believe it sent cancer drug developers a message, but I believe it's get tough approach will backfire:
1. Medicare and health plans will still continue to pay for Avastin.
2. Congress will hold oversight hearings and will rake Padzur over the coals (repeatedly) en route to amending FDA statute through one of many bills calling for faster access to new treatments.
3. The Obama administration will toss the FDA under the bus as the attacks target the President for presiding over the rationing of new drugs.
4. Cancer patients who moblilized to keep Avastin's label will become enraged and engaged long term.
5. The FDA has unleashed public sentiment that will overwhelm the medical progress haters -- Avorn, Angell, Wolfe, Goozner, Mahar, Soros, Furberg -- who will find their Congressional patrons have abandoned them.
What the FDA advisory panel (stacked by Richard Padzur, who heads up the Office of Cancer Drugs, with 6 advisors who wanted to yank Avastin last year) said was that based on the FDA's read of the data, Avastin despite causing a doubling in median progression free survival and objective response in tumors as well as an overall medial survival of two additional months in a subgroup of patients who were the most likely to die without Avastin (that's my take) and were more likely to die of cancer should not be used for breast cancer because it caused too much hypertension, bleeding and swelling.
Hal Barron, Executive Vice President, Head of Global Development: Oncology, Inflammation, and Virology at Genentech -- Avastin's creator -- summed up the FDA's (Padzur) deadly decision: The FDA (Padzur) would have allowed the Avastin indication to stay if it was really treating an unmet medical need. In otherwords, the FDA (Padzur) would have not stacked the deck against Avastin if the FDA (Padzur) thought that giving thousands of women longer life and better health.
The FDA switched the endpoints and oncologists, health plans and patients know it even as The Gooz oozes glee over the Avastin decision and derides the additional benefit to thousands of patients as just in their minds. Here's what Padzur said in his summary of evidence against Avastin.
"AVADO showed a statistically significant improvement in PFS for the bevacizumab-containing arms, with a HR of 0.70 (95% CI 0.55, 0.90) for 7.5 mg/kg
bevacizumab arm and HR of 0.62 (95% CI 0.48, 0.79) for the 15 mg/kg bevacizumab arm. The magnitude of treatment effect, as commonly assessed by clinicians based on
differences in median PFS, was marginal."
Genentech had called out this shifting of evidentiary standards in a pre-hearing summary of evidence:
"Although it was clear that AVADO and RIBBON1 (the two studies FDA, I mean Padzur, wanted to confirm the benefit of Avastin) were not powered to show an OS benefit, the agency now cites the studies for failing to show a statistically significant OS effect. Then, CDER stated only after its decision to withdraw Avastin’s MBC indication that any PFS effect “must confirm the magnitude of treatment effect of E2100."
Also: " CDER also has not articulated a clear rationale for its view that a 5.5-month improvement in median PFS is clinically meaningful but lesser improvements are not."
www.gene.com/gene/news/news-events/avastin/documents/051311.pdf
FDA might believe it sent cancer drug developers a message, but I believe it's get tough approach will backfire:
1. Medicare and health plans will still continue to pay for Avastin.
2. Congress will hold oversight hearings and will rake Padzur over the coals (repeatedly) en route to amending FDA statute through one of many bills calling for faster access to new treatments.
3. The Obama administration will toss the FDA under the bus as the attacks target the President for presiding over the rationing of new drugs.
4. Cancer patients who moblilized to keep Avastin's label will become enraged and engaged long term.
5. The FDA has unleashed public sentiment that will overwhelm the medical progress haters -- Avorn, Angell, Wolfe, Goozner, Mahar, Soros, Furberg -- who will find their Congressional patrons have abandoned them.
