Bayer and Onyx Pharmaceuticals stopped a study of their Nexavar lung cancer drug because the med failed to help patients live longer than standard treatment. An independent committee that monitored the trial advised the treatment wouldn't meet the main goal of the test, according to a
Bayer statement. Nexavar was in the last of three rounds of studies needed for regulatory approval for lung cancer.The monitoring committee stopped the test, which looked at more than 900 patients with non-small cell lung cancer, after finding a higher mortality rate in patients taking standard chemotherapy coupled with Nexavar then in those taking just standard chemotherapy alone. The drugmakers, however, didn't provide specifics on the deaths.
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, according to Bloomberg News, and help it compete against Roche and Genentech's Avastin, as well as ImClone's Erbitux.
"Nexavar was an important growth driver and this was the most important indication,'' Markus Metzger, an analyst at Vontobel in Cologne, tells Bloomberg. "The competitors, Erbitux and Avastin, are already waiting in the wings.''
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"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.