No clear evidence that most new cancer drugs extend or improve life

Even where drugs did show survival gains over existing treatments, these were often marginal, the results show.

Many of the drugs were approved on the basis of indirect ('surrogate') measures that do not always reliably predict whether a patient will live longer or feel better, raising serious questions about the current standards of drug regulation.

05 oct 2017--The researchers, based at King's College London and the London School of Economics say: "When expensive drugs that lack clinically meaningful benefits are approved and paid for within publicly funded healthcare systems, individual patients can be harmed, important societal resources wasted, and the delivery of equitable and affordable care undermined."
The research team analysed reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.
Of 68 cancer indications approved during this period, 57% (39) came onto the market on the basis of a surrogate endpoint and without evidence that they extended survival or improved the quality of patients' lives.
After a median of 5 years on the market, only an additional 8 drug indications had shown survival or quality of life gains.
Thus, out of 68 cancer indications approved by the EMA, and with a median 5 years follow-up, only 35 (51%) had shown a survival or quality of life gain over existing treatments or placebo. For the remaining 33 (49%), uncertainty remains over whether the drugs extend survival or improve quality of life.
The researchers outline some study limitations which could have affected their results, but say their findings raise the possibility that regulatory evidence standards "are failing to incentivise drug development that best meets the needs of patients, clinicians, and healthcare systems."
Taken together, these facts paint a sobering picture, says Vinay Prasad, Assistant Professor at Oregon Health & Science University in a linked editorial.
He calls for "rigorous testing against the best standard of care in randomized trials powered to rule in or rule out a clinically meaningful difference in patient centered outcomes in a representative population" and says "the use of uncontrolled study designs or surrogate endpoints should be the exception not the rule."
He adds: "The expense and toxicity of cancer drugs means we have an obligation to expose patients to treatment only when they can reasonably expect an improvement in survival or quality of life." These findings suggest "we may be falling far short of this important benchmark."
This study comes at a time when European governments are starting to seriously challenge the high cost of drugs, says Dr Deborah Cohen, Associate Editor at The BMJ, in an accompanying feature.
She points to examples of methodological problems with trials that EMA has either failed to identify or overlooked, including trial design, conduct, analysis and reporting.
"The fact that so many of the new drugs on the market lack good evidence that they improve patient outcomes puts governments in a difficult position when it comes to deciding which treatments to fund," she writes. "But regulatory sanctioning of a comparator that lacks robust evidence of efficacy, means the cycle of weak evidence and uncertainty continues."
In a patient commentary, Emma Robertson says: "It's clear to me and thousands of other patients like me that our current research and development model has failed."
Emma is leader of Just Treatment, a patient led campaign with no ties to the pharmaceutical industry, which is calling for a new system that rewards and promotes innovation, so that more effective and accessible cancer medicines are brought within reach.

More information: Availability of evidence on overall survival and quality of life benefits of cancer drugs approved by the European Medicines Agency: A retrospective cohort study of drug approvals from 2009-2013,www.bmj.com/content/359/bmj.j4530

Editorial: Do cancer drugs improve survival or quality of life? www.bmj.com/content/359/bmj.j4528

Patient commentary: the current model has failed, www.bmj.com/content/359/bmj.j4568

Feature: Cancer drugs: high price, uncertain value, www.bmj.com/content/359/bmj.j4543


Provided by British Medical Journal

Tests Could Predict Benefit From Cancer Drugs

By Amanda Gardner
30 oct 2008-- What if a blood test or biopsy could predict if a cancer therapy will help cure you, or only make you feel worse?
Tests like these, based on genes, proteins or other "molecular markers" may someday do just that for people battling colon, lung and pancreatic tumors, scientists reported at a news conference Tuesday.
"The ultimate goal is to bring personalized medicine to reality, to identify characteristics of tumors or patients where we can make a relatively dramatic impact using targeted agents," said Dr. Bruce Johnson of the Dana-Farber Cancer Institute and Harvard Medical School, in Boston.
Johnson moderated the teleconference, sponsored by the American Society of Clinical Oncology (ASCO). The briefing focused on research being presented at the second annual meeting on Molecular Markers in Cancer, which will take place Oct. 30 through Nov. 1 in Hollywood, Fla. The meeting is co-sponsored by ASCO, the U.S. National Cancer Institute and the European Organization for Research and Treatment of Cancer.
First up, colon cancer. Researchers pooled data from four clinical trials involving 715 patients. They confirmed that the cancer drug Vectibix (panitumumab) was only successful in treating advanced colorectal cancer in patients with the normal ("wild type") form of the KRAS gene -- not a mutated version.
Vectibix blocks the epidermal growth factor receptor (EGFR) on cancer cells.
The patient response rate to Vectibix was 14 percent if they carried the normal KRAS gene, but that rate sank to zero if the patient had a mutated form of the gene, said study lead author Daniel Freeman, a principal scientist in oncology research at Amgen Inc., which makes the drug.
Progression-free survival (3.3 months versus 1.7 months) and overall survival (8.3 months versus 5.7 months) were also better in patients with the normal KRAS gene.
This isn't the first time the KRAS gene has dictated just how well a cancer therapy might work. Just last week, researchers reported in the New England Journal of Medicine that colon cancer patients with a KRAS mutation would not respond to the drug Erbitux (cetuximab).
"The data is quite consistent that KRAS is an important negative predictor of patients unlikely to get a benefit from EGFR antibodies," Johnson said.
A second study discussed Tuesday focused on the predictive value of a marker for lung cancer, the No. 1 cancer killer in the United States.
Spanish researchers found that when both blood and tumor samples from patients with metastatic non-small cell lung cancer had a mutated form of the EGFR gene, the patients had a more aggressive cancer, with less time to live -- even after taking Tarceva (erlotinib), another targeted therapy that blocks EGFR.
It could be that more aggressive tumors lead to more mutant DNA in the blood, according to the researchers, from the Catalan Institute of Oncology in Barcelona.
The finding has practical implications for lung cancer patients, they noted. That's because blood samples could yield the same critical information as hard-to-obtain tissue samples, circumventing the need for biopsy. In fact, about a third of patients with this type of lung cancer don't yield enough tumor tissue to analyze for the mutation, the study authors said.
Finally, a third study looked at a particularly deadly malignancy, pancreatic cancer. Researchers found that patients whose pancreatic cancer tumors do not contain the S100A2 protein have double the life expectancy of patients whose tumors show high levels of the protein.
Testing for the presence of the protein beforehand could help select which patients would benefit from surgery. Such surgeries are difficult to perform and available to only a minority of patients with this type of cancer.
The protein may also provide a target for new treatments for this cancer killer, the team said.
The goal of all three studies are tests that could pinpoint which patients will reap the biggest benefit from a particular cancer therapy, Johnson said.
"Most of the pharmaceutical industry has been focused on making 100 percent of patients 20 percent better," he reasoned. "Today, we're talking about markers that can help 20 percent of patients get 100 percent better."