Merck (MRK +0.3%) announces that
Ervebo (Ebola Zaire Vaccine, Live) is now approved in Democratic
Republic of Congo, Burundi, Ghana and Zambia for prevention of disease
caused by Zaire ebolavirus in people at least 18 years old.
https://seekingalpha.com/news/3542292-merck-ebola-vaccine-okd-in-four-african-countries
Friday, February 14, 2020
PET Imaging Spots Prostate Cancer Metastases Missed on CT, MRI
More than a fourth of men with high-risk prostate cancer had lymph
node or distant metastases missed by CT or MRI but detected by PET
imaging targeting prostate specific membrane antigen (PSMA), a
prospective, multicenter study showed.
Biopsy-confirmed results showed that 72 of 268 (27%) had disease that had spread beyond the prostate. Almost 15% had locally advanced disease, and 12% had distant metastases. At study entry, conventional imaging with pelvic CT or MRI showed no evidence of regional or distant metastases in 96%-97% of the patients.
On the basis of image interpretation by three readers blinded to all clinical results, 18F-DCFPyL PET/CT had sensitivity of 31%-42% and specificity of 96%-99%. Sensitivity increased to as high as 63% with no loss of specificity when investigators excluded small lymph nodes known to be below the PET detection limit, as reported here at the Genitourinary Cancers Symposium.
“In men with high-risk prostate cancer who are candidates for radical prostatectomy and pelvic lymph node dissection, PET/CT with 18F-DCFPyL improved clinical N and M staging despite completely blinded image reads,” concluded Frédéric Pouliot, MD, of Laval University in Quebec City, Quebec. “Significant clinical information that was gained with 18F-DCFPyL PET imaging is likely to directly impact patient management.”
PSMA-targeted imaging has a strong biological rationale in that it is overexpressed in 94% of prostate cancers, including both primary and metastatic cancers, Jeremie Calais, MD, of the University of California Los Angeles, said during a review of PSMA PET imaging. Several PSMA-targeting PET tracers have been developed and all demonstrated superiority to CT and MRI — and to other PET tracers, such as choline and fluciclovine — for evaluating prostate cancer.
Asked who should undergo PSMA imaging, Calais said, “For sure, the high-risk prostate cancer patients and probably patients with a high suspicion of prostate cancer who have negative biopsies or equivocal MRI.”
PET-based imaging for prostate cancer has evolved in response to recognition that conventional imaging modalities are suboptimal for staging or restaging high-risk prostate cancer, said Pouliot. A variety of new tracers have been developed but have yet to be evaluated in prospective, multicenter, controlled trials with blinded review.
Previous studies showed PSMA-targeting PET/CT had sensitivity and specificity of 33%-100% and 80%-100%, respectively, Pouliot continued, but most of the data came from retrospective analyses or prospective single-center studies without central image assessment.
DCFPyL (PyL) is one of several 18F-labeled low-molecular-weight PET tracers that exhibits selective, high-affinity binding to PSMA. The imaging agent was evaluated prospectively in the multicenter OSPREY trial, which involved two patient cohorts: one with newly diagnosed high-risk prostate cancer and one with recurrent or metastatic prostate cancer. Pouliot reported findings from the patients with high-risk prostate cancer.
Conducted in the U.S. and Canada, the phase II/III trial had three central, independent PSMA PET/CT readers and one central reader for conventional imaging, all blinded to clinical and imaging results. The cohort included 268 men with high-risk prostate cancer, 252 of whom had evaluable DCFPyL PET/CT imaging results and evaluable pathologic findings from prostatectomy and pelvic lymph node dissection. The primary endpoint was specificity and sensitivity within the pelvic lymph nodes.
The 252 patients with complete information had a median age of 64 and median prostate specific antigen (PSA) level of 9.3 ng/mL. A third of the patients had T1 disease, 36.5% had T2 disease, and 26.6% had T3 cancers. Eight patients had N1 disease and one had M1 disease. Almost half of cancers were Gleason 8 and a third were Gleason 9.
The primary analysis yielded the following sensitivity and specificity by central reader:
Reanalysis that excluded 27 lymph nodes ≤5 mm yielded sensitivity of 62.9%, 48.6%, and 60.0% for the three independent readers and specificity of 97.9%, 98.9%, and 96.3%. PPV declined minimally and NPV increased by about 10 percentage points for each of the readers.
“At study entry, greater than 96% of the patients had no known regional or distant metastatic disease, based on conventional imaging,” said Pouliot. “A total of 72 of the 268 patients had [locally advanced or metastatic disease] detected on 18F-DCFPyL PET/CT.”
The PET/CT results showed that 39 patients had locally advanced disease and 33 had distant metastases.
Biopsy-confirmed results showed that 72 of 268 (27%) had disease that had spread beyond the prostate. Almost 15% had locally advanced disease, and 12% had distant metastases. At study entry, conventional imaging with pelvic CT or MRI showed no evidence of regional or distant metastases in 96%-97% of the patients.
On the basis of image interpretation by three readers blinded to all clinical results, 18F-DCFPyL PET/CT had sensitivity of 31%-42% and specificity of 96%-99%. Sensitivity increased to as high as 63% with no loss of specificity when investigators excluded small lymph nodes known to be below the PET detection limit, as reported here at the Genitourinary Cancers Symposium.
“In men with high-risk prostate cancer who are candidates for radical prostatectomy and pelvic lymph node dissection, PET/CT with 18F-DCFPyL improved clinical N and M staging despite completely blinded image reads,” concluded Frédéric Pouliot, MD, of Laval University in Quebec City, Quebec. “Significant clinical information that was gained with 18F-DCFPyL PET imaging is likely to directly impact patient management.”
PSMA-targeted imaging has a strong biological rationale in that it is overexpressed in 94% of prostate cancers, including both primary and metastatic cancers, Jeremie Calais, MD, of the University of California Los Angeles, said during a review of PSMA PET imaging. Several PSMA-targeting PET tracers have been developed and all demonstrated superiority to CT and MRI — and to other PET tracers, such as choline and fluciclovine — for evaluating prostate cancer.
Asked who should undergo PSMA imaging, Calais said, “For sure, the high-risk prostate cancer patients and probably patients with a high suspicion of prostate cancer who have negative biopsies or equivocal MRI.”
PET-based imaging for prostate cancer has evolved in response to recognition that conventional imaging modalities are suboptimal for staging or restaging high-risk prostate cancer, said Pouliot. A variety of new tracers have been developed but have yet to be evaluated in prospective, multicenter, controlled trials with blinded review.
Previous studies showed PSMA-targeting PET/CT had sensitivity and specificity of 33%-100% and 80%-100%, respectively, Pouliot continued, but most of the data came from retrospective analyses or prospective single-center studies without central image assessment.
DCFPyL (PyL) is one of several 18F-labeled low-molecular-weight PET tracers that exhibits selective, high-affinity binding to PSMA. The imaging agent was evaluated prospectively in the multicenter OSPREY trial, which involved two patient cohorts: one with newly diagnosed high-risk prostate cancer and one with recurrent or metastatic prostate cancer. Pouliot reported findings from the patients with high-risk prostate cancer.
Conducted in the U.S. and Canada, the phase II/III trial had three central, independent PSMA PET/CT readers and one central reader for conventional imaging, all blinded to clinical and imaging results. The cohort included 268 men with high-risk prostate cancer, 252 of whom had evaluable DCFPyL PET/CT imaging results and evaluable pathologic findings from prostatectomy and pelvic lymph node dissection. The primary endpoint was specificity and sensitivity within the pelvic lymph nodes.
The 252 patients with complete information had a median age of 64 and median prostate specific antigen (PSA) level of 9.3 ng/mL. A third of the patients had T1 disease, 36.5% had T2 disease, and 26.6% had T3 cancers. Eight patients had N1 disease and one had M1 disease. Almost half of cancers were Gleason 8 and a third were Gleason 9.
The primary analysis yielded the following sensitivity and specificity by central reader:
- Reader 1 – 41.9%, 97.9%
- Reader 2 – 30.6%, 98.9%
- Reader 3 – 40.3%, 96.3%
Reanalysis that excluded 27 lymph nodes ≤5 mm yielded sensitivity of 62.9%, 48.6%, and 60.0% for the three independent readers and specificity of 97.9%, 98.9%, and 96.3%. PPV declined minimally and NPV increased by about 10 percentage points for each of the readers.
“At study entry, greater than 96% of the patients had no known regional or distant metastatic disease, based on conventional imaging,” said Pouliot. “A total of 72 of the 268 patients had [locally advanced or metastatic disease] detected on 18F-DCFPyL PET/CT.”
The PET/CT results showed that 39 patients had locally advanced disease and 33 had distant metastases.
Disclosures
The study was supported by Progenics Pharmaceuticals.
Pouliot did not report disclosures.
Pouliot did not report disclosures.
Primary Source
Genitourinary Cancers Symposium
https://www.medpagetoday.com/meetingcoverage/mgucs/8489221 States Reject $18B Offer From Drug Wholesalers to Settle Opioid Litigation
An $18 billion settlement offer from three major drug wholesalers
aimed at resolving litigation over their alleged role in the opioid
crisis has fallen apart, after more than 20 state attorneys general
rejected it in a letter sent to the companies’ law firms earlier this
week.
The letter, reviewed by The Wall Street Journal, shows that the drug industry hasn’t won enough support from states to begin moving the sprawling litigation to a global resolution.
The dissenting states want the wholesalers to contribute between $22 billion and $32 billion, according to a person familiar with the matter.
The rejection is the latest setback in negotiations to resolve the nation’s complex opioid-crisis litigation, which began several years ago. The majority of the lawsuits have been consolidated in federal court in Cleveland, though state attorneys general have largely pursued cases in their own state courts.
The parties have been holding talks since at least October, when The Wall Street Journal reported that the three distributors — McKesson Corp., AmerisourceBergen Corp., and Cardinal Health Inc. — were in talks to collectively pay $18 billion over 18 years. Johnson & Johnson was also involved in the discussions to contribute additional money, the Journal reported.
The letter was signed by attorneys general for 21 states as well as Puerto Rico and the District of Columbia and include some of the hardest hit by the opioid crisis, including Ohio and West Virginia.
AmeriSourceBergen said it remains committed to a “fair negotiated resolution” but will continue to defend itself in court and is preparing for upcoming trials. It said in a statement it was “disappointed to hear that some states do not currently understand the merits of the global settlement framework that the distributors have been discussing with the attorneys’ general over the past many months.”
McKesson said it is focused on “finalizing a global settlement structure that would serve as the best path forward to provide billions of dollars in immediate funding and relief to states and local communities.” The company said it is committed to be part of a solution but is prepared to defend itself in litigation.
Cardinal Health didn’t respond to a request for comment.
Ohio Attorney General Dave Yost said in an interview the letter shows the states “who are not willing to sign on” to the settlement. He said the wholesalers should pay their $18 billion in a shorter time period or provide more funding.
The letter is signed mostly by Democratic attorneys general, although there are some Republicans, including West Virginia’s Patrick Morrissey and Florida’s Ashley Moody.
“Each of you has expressed that your clients seek a settlement that is global,” the letter reads. “It is our collective view that the most recently communicated offer is unlikely to achieve that goal. We invite you to discuss our specific issues more fully so that a global settlement may be reached.”
https://www.marketscreener.com/MCKESSON-CORPORATION-13470/news/21-States-Reject-18-Billion-Offer-From-Drug-Wholesalers-to-Settle-Opioid-Litigation-Update-30000564/
The letter, reviewed by The Wall Street Journal, shows that the drug industry hasn’t won enough support from states to begin moving the sprawling litigation to a global resolution.
The dissenting states want the wholesalers to contribute between $22 billion and $32 billion, according to a person familiar with the matter.
The rejection is the latest setback in negotiations to resolve the nation’s complex opioid-crisis litigation, which began several years ago. The majority of the lawsuits have been consolidated in federal court in Cleveland, though state attorneys general have largely pursued cases in their own state courts.
The parties have been holding talks since at least October, when The Wall Street Journal reported that the three distributors — McKesson Corp., AmerisourceBergen Corp., and Cardinal Health Inc. — were in talks to collectively pay $18 billion over 18 years. Johnson & Johnson was also involved in the discussions to contribute additional money, the Journal reported.
The letter was signed by attorneys general for 21 states as well as Puerto Rico and the District of Columbia and include some of the hardest hit by the opioid crisis, including Ohio and West Virginia.
AmeriSourceBergen said it remains committed to a “fair negotiated resolution” but will continue to defend itself in court and is preparing for upcoming trials. It said in a statement it was “disappointed to hear that some states do not currently understand the merits of the global settlement framework that the distributors have been discussing with the attorneys’ general over the past many months.”
McKesson said it is focused on “finalizing a global settlement structure that would serve as the best path forward to provide billions of dollars in immediate funding and relief to states and local communities.” The company said it is committed to be part of a solution but is prepared to defend itself in litigation.
Cardinal Health didn’t respond to a request for comment.
Ohio Attorney General Dave Yost said in an interview the letter shows the states “who are not willing to sign on” to the settlement. He said the wholesalers should pay their $18 billion in a shorter time period or provide more funding.
The letter is signed mostly by Democratic attorneys general, although there are some Republicans, including West Virginia’s Patrick Morrissey and Florida’s Ashley Moody.
“Each of you has expressed that your clients seek a settlement that is global,” the letter reads. “It is our collective view that the most recently communicated offer is unlikely to achieve that goal. We invite you to discuss our specific issues more fully so that a global settlement may be reached.”
https://www.marketscreener.com/MCKESSON-CORPORATION-13470/news/21-States-Reject-18-Billion-Offer-From-Drug-Wholesalers-to-Settle-Opioid-Litigation-Update-30000564/
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