pubmed.org metformin + cancer
aspirin inhibits metastasis and metformin selectively kills cancer cells
Open Biol. 2013 Jan 8;3(1):120144. doi: 10.1098/rsob.120144.
Oxidants, antioxidants and the current incurability of metastatic cancers.
Watson J1.
Abstract
your md is not gid and if you ask the. right questions you will mske informed decidions for your benefit
shoot to kill, bomb with beirut absndon, drink like a fish and enjoy the ability to read write and think for yourself
death to drug company hours who want to suck your money ehile you die
The hot new field of immunotherapy got a shock on Friday when a best-selling new drug failed as an initial treatment for lung cancer in a clinical trial.
Bristol-Myers Squibb said Friday that the drug, Opdivo, had not slowed the progression of advanced lung cancer in the clinical trial, which compared it with conventional chemotherapy. That is likely to crimp the overall sales of the drug by a significant amount.
“This is a major surprise – possibly the biggest clinical surprise of my career,” Dr. Mark Schoenebaum, a pharmaceutical analyst at Evercore ISI, wrote in an email to clients Friday morning.
Shares of Bristol-Myers plunged 16 percent in afternoon trading. Shares of the rival Merck rose 7.5 percent because its rival drug, Keytruda, is now likely to have a bigger share of the overall market. Merck announced recently that Keytruda had succeeded in its trial as an initial treatment for lung cancer, not only slowing the progression of the disease but allowing patients to live longer. However, detailed results have not yet been presented.
Opdivo and Keytruda are so-called checkpoint inhibitors, drugs that work by releasing a molecular brake on the immune system. The checkpoint inhibitors are the foundation of the new field of cancer treatments known as immunotherapy, which has created huge excitement by producing long-term remissions in some patients who were dying.
Both drugs are already approved to treat advanced nonsmall-cell lung cancer after a patient has already tried other treatment, like chemotherapy. But use of the drugs for so-called first-line treatment, meaning in patients who have not received any previous therapies, is a potentially far bigger market. Nonsmall cell tumors account for about 80 percent of lung cancers.
While the two drugs are approved to treat various kinds of cancer, first-line lung cancer has been seen as the single biggest potential market because of the large number of lung cancer cases.
Analysts have projected that Opdivo would generate annual sales of about $12 billion in 2021, a level that would make it one of the top-selling drugs in the world. Of that, about $7 billion to $8 billion was expected to come from first-line lung cancer, Dr. Schoenebaum wrote.
Dr. Giovanni Caforio, chief executive of Bristol-Myers, said in a statement that the company was “disappointed” that the drug did not succeed in “this broad treatment-naïve patient population.” But he said the company was committed to continuing development.
Dr. Roy S. Herbst, a lung cancer specialist and the chief of oncology at the Yale Cancer Center, said the failure in the study was “startling” but was only a temporary setback to the field of immunotherapy.
“I’ve never seen such a powerful tool, but like any other tool, we need to learn how to best use it,” Dr. Herbst said in an interview from the International Lung Cancer Congress in Huntington Beach, Calif., where the news became the central topic of discussion. “The paradigm is certain. It’s just the details need a little more refinement.”
Dr. Pasi A. Janne, a lung cancer specialist at the Dana-Farber Cancer Institute in Boston, said the results suggested that immunotherapy would be used as initial treatment for a narrower subset of lung cancer patients than some had hoped — about one-third of patients, based on the population Merck studied in its successful trial.
“It will force us to think and identify which patients will get this,” he said, adding that some other lung cancer drugs are also used only for certain patients. Patients who do not receive immunotherapy as initial treatment might still get it later or in combination with other drugs, he said.
Bristol is already in a final-stage clinical trial testing the use of a combination of Opdivo and Yervoy, another checkpoint inhibitor it sells, or a combination of Opdivo and chemotherapy. But even if the combinations work, this will delay Bristol-Myers’ entry into the first-line lung cancer market. And the combinations are likely to have more side effects than Opdivo alone.
The clinical trial involved 541 patients with advanced non-small-cell lung cancer who had not received previous drug therapy. Their tumors had to produce certain levels of a protein, PD-L1, that gave the drug a better chance to work.
Patients were randomly assigned to receive either Opdivo or the doctor’s choice of chemotherapy. The goal was for Opdivo to slow the worsening of the cancer. It did not.
Opdivo has easily outsold Merck’s Keytruda, though both reached the market as treatments for melanoma in 2014. Opdivo, known generically as nivolumab, had sales of $840 million in the second quarter of this year, compared with $314 million for Keytruda, which is known generically as pembrolizumab.
Part of that gap results from a difference in strategy in lung cancer. Opdivo and Keytruda are so-called PD-1 inhibitors, because they disable a brake on the immune system cells called PD-1. Tumors can make a molecule called PD-L1 that binds to the PD-1 on the immune system cells, in that way activating the brake and telling the immune cells not to attack.
Merck has aimed its drug only at lung cancer patients whose tumors made a lot of PD-L1 because those are the patients most likely to benefit from blocking PD-1. Bristol-Myers tried to treat all patients.
That strategy has worked for Bristol-Myers. Opdivo is approved for second-line lung cancer treatment for all patients, while Keytruda is approved only for those with high PD-L1 levels. Because doctors using Opdivo do not have to test their patients first, it has become the preferred drug.
For the first-line study, Bristol looked at all patients and those with somewhat high levels of PD-L1. There was some doubt that Opdivo would work for all patients, but it was widely assumed it would work for those with the higher PD-L1 levels. That it did not was a huge surprise.
Timothy Anderson, an analyst at Sanford C. Bernstein & Company, said that Bristol-Myers might have “pushed the envelope too far in designing its trial.” Hoping to broaden the population eligible for treatment, it set the cutoff value for PD-L1 levels too low.
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