Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals have stopped a late stage trial of their cancer drug Nexavar (sorafenib) in patients with nonsmall-cell lung cancer (NSCLC), because it was not showing the hoped for increase in survival.
Following a planned interim analysis, the trial's independent data monitoring committee (DMC) concluded that the drug was not going to meet the trial's main goal of improving overall survival.
In the phase 3 trial, a group of patients with squamous cell carcinoma of the lung who took the drug in combination with chemotherapy drugs carboplatin and paclitaxel showed a higher rate of death than a group that received chemotherapy alone.
The trial, which is called ESCAPE (Evaluation of Sorafenib, Carboplatin And Paclitaxel Efficacy in NSCLC), was otherwise showing safety events generally in line with those previously reported, said Bayer in a press statement.
The two drug companies are giving the DMC information to health authorities and other investigators studying the effects of Nexavar and will also be presenting the findings of the trial at a forthcoming scientific meeting.
The companies will also be reviewing the findings of this trial, including the DMC review, to see if they impact any other ongoing lung cancer trials using Nexavar.
Vice president of Therapeutic Area Oncology at Bayer HealthCare Pharmaceuticals, Dr Susan Kelley said that they were disappointed with this result, but the two companies were still very much committed to widening the scope of Nexavar in treating as many cancers as possible and will continue to extend trials to other cancers.
"Nexavar has proven significant clinical benefit for patients with liver cancer and advanced kidney cancer and we will continue to investigate its potential across a wide variety of tumors," said Kelley.
The ESCAPE study was a multicentre, randomized, double-blind, placebo controlled phase 3 trial involving more than 900 NSCLC patients at over 140 clinics in North and South America, Europe and Asia.
The main outcome sought was overall survival, but secondary endpoints included progression-free survival, tumour response, quality of life, and drug safety.
The participants had not received any systematic anti-cancer treatment for lung cancer before the trial, which was open to patients with all types of NSCLC, including squamous cell carcinoma or adenocarcinomas.
The patients were randomized to a drug group and a control (placebo) group. The drug group was given 400 mg of Nexavar, orally, twice a day, while the control group had a placebo. Both groups also had two chemotherapy drugs, carboplatin and paclitaxel. Both groups continued with the drug or placebo alone, after chemotherapy had finished (maintenance phase), until symptoms of tumour progression or side effects showed.
Nexavar (sorafenib) attacks both the tumour cell and the blood vessels that feed it. In studies before clinical trials, the drug showed ability to target kinase proteins thought to be involved in cell growth and development of blood supply, two essential cancer enablers. The kinases involved include: Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.
Nexavar is approved for the treatment of liver cancer in over 30 countries and for the treatment of advanced kidney cancer in over 60 countries. It is being evaluated for use with many other cancers such as breast cancer, metastatic melanoma, and as an adjuvant therapy for kidney cancer and liver cancer.
Sorafenib (Nexavar) Dropped From Lung Cancer Trial
Categories Cancer / Oncology, Lung
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2 comentarios:
"Nexavar is already approved in more than 30 countries for liver cancer and in more than 60 countries for the treatment of patients with advanced kidney cancer. But an additional indication for lung cancer would push it past the $1 billion sales mark."
The FDA easily approves a drug by “indication” (why is it that you’re going to take the drug). A drug company presents a drug and wants approval for two or three different indications. One may be really insignificant, affecting a very small number of people (lung cancer). The major indication might affect millions of people (liver and/or kidney cancer).
The drug doesn’t necessarily show efficacy for the lung cancer indication, but they’re able to get it approved for the liver and/or kidney cancer indication, while the FDA and the drug company both know the drug is going to be used for that all indications.
It’s going to be used “off-label" for lung cancer. The FDA should be intervening, but they don’t. The the FDA says that they don’t regulate the “off-label” use of drugs, and allows it to happen, and the “off-label” use of the drug becomes a public health threat. Nexavar, in combination with standard therapy, kills more patients than standard therapy alone.
Combination chemotherapy has not always produced greater degrees of clinical benefit than single agent therapy, as this clinical trial illustrates. When two or more drugs are given, there is a greater probability that at least one of the drugs will be active. There is then the potential for true synergery, where the whole is greater than the sum of the parts.
But most drug combinations are only additive or at most, minimally synergistc. However, some newer combinations show greater degrees of synergy, although apparently not in this study. True synergy is rather uncommon in most adult solid tumors. Most drug combinations in diseases are merely additive, where the whole equals the sum of its parts, and not synergistic. In hematologic neoplasms (leukemia, lymphoma, multiple myeloma), true synergy is very common.
In cases like this study, where drugs are only additive and not synergistic, nothing is learned by testing the drugs in combination compared to what is learned by testing them separately. Therefore, drugs in combination are only tested in cases where there is the realistic possiblitiy of seeing true synergy.
The best combinations are those in which there is true synergy and in which the toxicities of the drugs in the combination are non-overlapping, so that full doses of each drug may be given safely.
The era of empiric, aggressive, multi-agent cytotoxic chemotherapy for first-line/recurrent/refractory adult solid tumors should come to an end.
More emphasis should be put on matching treatment to patient, through the use of individualized genetic and cellular pre-testing, having more respect for minimal partial response or stable disease, when it can be achieved through use of the least toxic and mutagenic drug regimens, and reserve the use of higher dose therapy or aggressive combination chemotherapy to those patients with tumor biologies most amenable to attack and destroy by these aggressive treatments.
Greg:
I agree with you
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