The information available on the Breast Cancer Network Australia website is not medical advice and is provided for information purposes only. It should not be viewed as a replacement for a consultation with a qualified medical professional. Our website is designed to offer information and support to the general public. Be aware that we do not provide any medical advice, and for medical advice we recommend you speak to a qualified medical professional or doctor. 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Drugs Approved Quickly Often Fail To Measure Up Later","id":"message:139563","revisionNum":1,"repliesCount":3,"author":{"__ref":"User:user:21666"},"depth":0,"hasGivenKudo":false,"board":{"__ref":"Forum:board:general-treatment-and-surgery"},"conversation":{"__ref":"Conversation:conversation:139563"},"readOnly":false,"editFrozen":false,"moderationData":{"__ref":"ModerationData:moderation_data:139563"},"body@stripHtml({\"truncateLength\":200})":"Online article published 28 May 2019 https://www.npr.org/sections/health-shots/2019/05/28/727598045/cancer-drugs-approved-quickly-often-fail-to-measure-up-later?utm_source=Color+Client+Newsletter&utm...","body@stringLength":"8191","rawBody":"Online article published 28 May 2019 https://www.npr.org/sections/health-shots/2019/05/28/727598045/cancer-drugs-approved-quickly-often-fail-to-measure-up-later?utm_source=Color+Client+Newsletter&utm_campaign=d0ae11a21f-Spectrum_6_2019&utm_medium=email&utm_term=0_07102bacdf-d0ae11a21f-226561061
\n\n
Cancer drugs that speed onto the\nmarket based on encouraging preliminary studies often don't show clear benefits\nwhen more careful follow-up trials are done, according to research published\nTuesday.
\n\n
These cancer drugs are granted\naccelerated approval to give patients faster access to the treatments and to\nallow drug companies to reap the economic rewards sooner. As a condition of\nthis process, the Food and Drug Administration requires drug companies to\nconduct more research, to confirm whether the medications actually work and are\nsafe.
In\nthe follow-up studies, only 19 of the 93 drugs clearly extended the lives of\nthe patients taking them, according to the study, published in the latest JAMA Internal Medicine.
\n\n
For example, Genentech's Avastin, or\nbevacizumab, won accelerated approval to treat the deadly brain cancer\nglioblastoma, but the drug did not extend the lives of patients in a follow-up\nstudy.
\n\n
Sometimes patients value drugs\nbecause they improve their quality of life. This drug didn't do that either,\nyet the FDA left it on the market as an approved treatment for glioblastoma.
\n\n
\"So that was the most baffling\nthing,\" says Bishal Gyawali, an oncologist on the research team. \"I\nfind it very difficult to understand.\"
\n\n
The researchers said follow-up\nstudies for these cancer drugs often didn't even use overall survival or\nimproved quality of life as the benchmark.
\n\n
Instead,\nmany used the same measure that formed the basis for their preliminary approval\n— for example, tumor shrinkage. Those targets, called \"surrogate endpoints,\" often don't predict who will\nlive longer or more comfortably.
\n\n
\"How can we use the same\nsurrogate endpoint and say they have clinical benefit in a confirmatory\ntrial?\" Gyawali asks, when that endpoint clearly wasn't sufficient for\nfull approval of the drug at the outset. (Gyawali is now at Queens University\nin Ontario.)
\n\n
\"The reason for giving these\napprovals should be transparent,\" he says, but the FDA doesn't explain its\nreasoning.
\n\n
A second study in the same issue looked at cancer\ndrugs approved based on a specific surrogate endpoint called \"response\nrate.\" Response to a drug can be anything from spectacular and complete\nremission to weak and transitory shrinkage of a tumor. And these responses\ndon't necessarily mean people will live longer or be more comfortable.
\n\n
The study looked at 59 cancer drugs\napproved initially on the basis of their response rate and found that just six\neventually won regular approval based on their overall survival benefit.
\n\n
Studies based on response rate don't\ninclude a comparison group, so the scientists at Oregon Health and Science\nUniversity argue that it's difficult to say whether these new drugs are better\nthan other drugs already on the market.
\n\n
Sometimes\nthere is no comparison group because these are rare cancers, or the drug\ntargets a rare mutation in a common cancer, so it's difficult to pull together\na study that randomizes patients into different treatment groups, says Dr. Richard Schilsky, the senior vice president and\nchief medical officer at the American Society of Clinical Oncology.
\n\n
But for other circumstances, \"if\nwe put the investment in it we would be able to do randomized controlled\ntrials,\" says Emerson Chen, an oncology fellow at OHSU. Those studies\noften add another year or more to a follow-up study, he says, but he advocates\nfor them because they provide \"more definitive information about the\nsurvival and the patient-reported outcomes.\"
\n\n
\"One\nof the reasons we don't do those kinds of studies is that people say these drugs\nare so potent it would be wrong to do those kinds of studies ... ethically or\npractically,\" says oncologist Vinay Prasad, senior author of the paper. \"But I\nthink what we find is these drugs unfortunately are not that potent.\"
\n\n
In a commentary, Dr. Ezekiel Emmanuel and colleagues at\nthe University of Pennsylvania write that there \"is no good reason for the\nFDA to rely so heavily on accelerated approval using response rates or other\nunreliable surrogate end points.\"
\n\n
\"Drugs with unproven\neffectiveness sell false hope to desperate patients, who are likely paying\nthousands of dollars out of pocket for them,\" they write, adding,\n\"Approval of ineffective drugs also crowds out innovation that might\nproduce effective treatment.\"
\n\n
The FDA gets pressure both from\npatients and from drug companies to accelerate approval of new cancer drugs and\nconstantly needs to strike a balance between innovation and caution, ASCO's\nSchilsky says.
\n\n
Randomized trials are the gold\nstandard for cancer research, but he says they can be challenging if a drug is\nalready on the market.
\n\n
\"When the preliminary results\nwith some of these new treatments are looking very promising, it's particularly\ndifficult to get patients to accept randomization to a standard therapy that\nmay be far inferior — or at least appear to be far inferior — to the new\ntreatment,\" Schilsky says.
\n\n
He also pushes back against the\n\"sweeping generalizations\" in these two studies. \"Regulatory\ndecisions have to be made on a case by case basis and in a particular\ncontext,\" he says. But he agrees that the FDA should be more transparent\nabout its decisions, so scientists can better understand them.
\n\n
The FDA did not provide NPR with\ndetails about its decision to leave Avastin on the market for brain cancer. In\na statement, an agency spokeswoman notes that the FDA weighs risk and benefits,\nsaying, \"It has been widely accepted that benefit can be demonstrated by a\nnumber of endpoints, not just overall survival.\"
\n\n
You\ncan contact NPR science correspondent Richard Harris at rharris@npr.org.
\n ","kudosSumWeight":1,"postTime":"2019-06-29T17:21:07.000-07:00","images":{"__typename":"AssociatedImageConnection","edges":[],"totalCount":0,"pageInfo":{"__typename":"PageInfo","hasNextPage":false,"endCursor":null,"hasPreviousPage":false,"startCursor":null}},"attachments":{"__typename":"AttachmentConnection","pageInfo":{"__typename":"PageInfo","hasNextPage":false,"endCursor":null,"hasPreviousPage":false,"startCursor":null},"edges":[]},"tags":{"__typename":"TagConnection","pageInfo":{"__typename":"PageInfo","hasNextPage":false,"endCursor":null,"hasPreviousPage":false,"startCursor":null},"edges":[{"__typename":"TagEdge","cursor":"MjUuMnwyLjF8b3wxMHxfTlZffDE","node":{"__typename":"Tag","id":"tag:clinical-trials","text":"clinical-trials","time":"2025-03-25T05:02:18.515-07:00","lastActivityTime":null,"messagesCount":null,"followersCount":null}}]},"timeToRead":4,"currentRevision":{"__ref":"Revision:revision:139563_1"},"latestVersion":null,"metrics":{"__typename":"MessageMetrics","views":71},"visibilityScope":"PUBLIC","canonicalUrl":null,"seoTitle":null,"seoDescription":null,"isEscalated":null,"placeholder":false,"originalMessageForPlaceholder":null,"messagePolicies":{"__typename":"MessagePolicies","canModerateSpamMessage":{"__typename":"PolicyResult","failureReason":{"__typename":"FailureReason","message":"error.lithium.policies.feature.moderation_spam.action.moderate_entity.allowed.accessDenied","key":"error.lithium.policies.feature.moderation_spam.action.moderate_entity.allowed.accessDenied","args":[]}}},"archivalData":null,"customFields":[],"body":"Online article published 28 May 2019 https://www.npr.org/sections/health-shots/2019/05/28/727598045/cancer-drugs-approved-quickly-often-fail-to-measure-up-later?utm_source=Color+Client+Newsletter&utm_campaign=d0ae11a21f-Spectrum_6_2019&utm_medium=email&utm_term=0_07102bacdf-d0ae11a21f-226561061
\n\n
Cancer drugs that speed onto the\nmarket based on encouraging preliminary studies often don't show clear benefits\nwhen more careful follow-up trials are done, according to research published\nTuesday.
\n\n
These cancer drugs are granted\naccelerated approval to give patients faster access to the treatments and to\nallow drug companies to reap the economic rewards sooner. As a condition of\nthis process, the Food and Drug Administration requires drug companies to\nconduct more research, to confirm whether the medications actually work and are\nsafe.
In\nthe follow-up studies, only 19 of the 93 drugs clearly extended the lives of\nthe patients taking them, according to the study, published in the latest JAMA Internal Medicine.
\n\n
For example, Genentech's Avastin, or\nbevacizumab, won accelerated approval to treat the deadly brain cancer\nglioblastoma, but the drug did not extend the lives of patients in a follow-up\nstudy.
\n\n
Sometimes patients value drugs\nbecause they improve their quality of life. This drug didn't do that either,\nyet the FDA left it on the market as an approved treatment for glioblastoma.
\n\n
\"So that was the most baffling\nthing,\" says Bishal Gyawali, an oncologist on the research team. \"I\nfind it very difficult to understand.\"
\n\n
The researchers said follow-up\nstudies for these cancer drugs often didn't even use overall survival or\nimproved quality of life as the benchmark.
\n\n
Instead,\nmany used the same measure that formed the basis for their preliminary approval\n— for example, tumor shrinkage. Those targets, called \"surrogate endpoints,\" often don't predict who will\nlive longer or more comfortably.
\n\n
\"How can we use the same\nsurrogate endpoint and say they have clinical benefit in a confirmatory\ntrial?\" Gyawali asks, when that endpoint clearly wasn't sufficient for\nfull approval of the drug at the outset. (Gyawali is now at Queens University\nin Ontario.)
\n\n
\"The reason for giving these\napprovals should be transparent,\" he says, but the FDA doesn't explain its\nreasoning.
\n\n
A second study in the same issue looked at cancer\ndrugs approved based on a specific surrogate endpoint called \"response\nrate.\" Response to a drug can be anything from spectacular and complete\nremission to weak and transitory shrinkage of a tumor. And these responses\ndon't necessarily mean people will live longer or be more comfortable.
\n\n
The study looked at 59 cancer drugs\napproved initially on the basis of their response rate and found that just six\neventually won regular approval based on their overall survival benefit.
\n\n
Studies based on response rate don't\ninclude a comparison group, so the scientists at Oregon Health and Science\nUniversity argue that it's difficult to say whether these new drugs are better\nthan other drugs already on the market.
\n\n
Sometimes\nthere is no comparison group because these are rare cancers, or the drug\ntargets a rare mutation in a common cancer, so it's difficult to pull together\na study that randomizes patients into different treatment groups, says Dr. Richard Schilsky, the senior vice president and\nchief medical officer at the American Society of Clinical Oncology.
\n\n
But for other circumstances, \"if\nwe put the investment in it we would be able to do randomized controlled\ntrials,\" says Emerson Chen, an oncology fellow at OHSU. Those studies\noften add another year or more to a follow-up study, he says, but he advocates\nfor them because they provide \"more definitive information about the\nsurvival and the patient-reported outcomes.\"
\n\n
\"One\nof the reasons we don't do those kinds of studies is that people say these drugs\nare so potent it would be wrong to do those kinds of studies ... ethically or\npractically,\" says oncologist Vinay Prasad, senior author of the paper. \"But I\nthink what we find is these drugs unfortunately are not that potent.\"
\n\n
In a commentary, Dr. Ezekiel Emmanuel and colleagues at\nthe University of Pennsylvania write that there \"is no good reason for the\nFDA to rely so heavily on accelerated approval using response rates or other\nunreliable surrogate end points.\"
\n\n
\"Drugs with unproven\neffectiveness sell false hope to desperate patients, who are likely paying\nthousands of dollars out of pocket for them,\" they write, adding,\n\"Approval of ineffective drugs also crowds out innovation that might\nproduce effective treatment.\"
\n\n
The FDA gets pressure both from\npatients and from drug companies to accelerate approval of new cancer drugs and\nconstantly needs to strike a balance between innovation and caution, ASCO's\nSchilsky says.
\n\n
Randomized trials are the gold\nstandard for cancer research, but he says they can be challenging if a drug is\nalready on the market.
\n\n
\"When the preliminary results\nwith some of these new treatments are looking very promising, it's particularly\ndifficult to get patients to accept randomization to a standard therapy that\nmay be far inferior — or at least appear to be far inferior — to the new\ntreatment,\" Schilsky says.
\n\n
He also pushes back against the\n\"sweeping generalizations\" in these two studies. \"Regulatory\ndecisions have to be made on a case by case basis and in a particular\ncontext,\" he says. But he agrees that the FDA should be more transparent\nabout its decisions, so scientists can better understand them.
\n\n
The FDA did not provide NPR with\ndetails about its decision to leave Avastin on the market for brain cancer. In\na statement, an agency spokeswoman notes that the FDA weighs risk and benefits,\nsaying, \"It has been widely accepted that benefit can be demonstrated by a\nnumber of endpoints, not just overall survival.\"
\n\n
You\ncan contact NPR science correspondent Richard Harris at rharris@npr.org.
\n "},"Conversation:conversation:139563":{"__typename":"Conversation","id":"conversation:139563","solved":false,"topic":{"__ref":"ForumTopicMessage:message:139563"},"lastPostingActivityTime":"2019-06-29T19:54:38.000-07:00","lastPostTime":"2019-06-29T19:54:38.000-07:00","unreadReplyCount":3,"isSubscribed":false},"ModerationData:moderation_data:139563":{"__typename":"ModerationData","id":"moderation_data:139563","status":"APPROVED","rejectReason":null,"isReportedAbuse":false,"rejectUser":null,"rejectTime":null,"rejectActorType":null},"Revision:revision:139563_1":{"__typename":"Revision","id":"revision:139563_1","lastEditTime":"2019-06-29T17:21:07.000-07:00"},"ForumReplyMessage:message:139566":{"__typename":"ForumReplyMessage","id":"message:139566","conversation":{"__ref":"Conversation:conversation:139563"},"author":{"__ref":"User:user:18211"},"revisionNum":1,"uid":139566,"depth":1,"hasGivenKudo":false,"subscribed":false,"board":{"__ref":"Forum:board:general-treatment-and-surgery"},"subject":"Re: Cancer Drugs Approved Quickly Often Fail To Measure Up Later","readOnly":false,"editFrozen":false,"moderationData":{"__ref":"ModerationData:moderation_data:139566"},"parent":{"__ref":"ForumTopicMessage:message:139563"},"body":"Certainly helps us understand why things take so long yo be approved.","body@stringLength":"69","rawBody":"Certainly helps us understand why things take so long yo be approved.","kudosSumWeight":0,"repliesCount":0,"postTime":"2019-06-29T19:54:38.000-07:00","images":{"__typename":"AssociatedImageConnection","edges":[],"totalCount":0,"pageInfo":{"__typename":"PageInfo","hasNextPage":false,"endCursor":null,"hasPreviousPage":false,"startCursor":null}},"attachments":{"__typename":"AttachmentConnection","pageInfo":{"__typename":"PageInfo","hasNextPage":false,"endCursor":null,"hasPreviousPage":false,"startCursor":null},"edges":[]},"timeToRead":1,"currentRevision":{"__ref":"Revision:revision:139566_1"},"latestVersion":null,"metrics":{"__typename":"MessageMetrics","views":0},"visibilityScope":"PUBLIC","isEscalated":null,"placeholder":false,"originalMessageForPlaceholder":null,"messagePolicies":{"__typename":"MessagePolicies","canModerateSpamMessage":{"__typename":"PolicyResult","failureReason":{"__typename":"FailureReason","message":"error.lithium.policies.feature.moderation_spam.action.moderate_entity.allowed.accessDenied","key":"error.lithium.policies.feature.moderation_spam.action.moderate_entity.allowed.accessDenied","args":[]}}},"customFields":[],"replies":{"__typename":"MessageConnection","edges":[],"pageInfo":{"__typename":"PageInfo","hasNextPage":false,"endCursor":null,"hasPreviousPage":false,"startCursor":null}}},"CachedAsset:theme:customTheme1-1743643394041":{"__typename":"CachedAsset","id":"theme:customTheme1-1743643394041","value":{"id":"customTheme1","animation":{"fast":"150ms","normal":"250ms","slow":"500ms","slowest":"750ms","function":"cubic-bezier(0.07, 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