An experimental breast cancer drug from Roche Holding AG (ROG) that carries chemotherapy directly into malignant cells while bypassing healthy ones delayed tumors longer and with fewer side effects than an established therapy.
The treatment, combining Roche’s Herceptin with an older chemotherapy medicine, delayed progression of tumors 3.2 months longer than GlaxoSmithKline Plc (GSK)’s Tykerb with chemotherapy in women with advanced disease. The data is being reported today at the American Society of Clinical Oncology meeting in Chicago.
More patients on the drug, dubbed T-DM1, were alive after two years, though the difference fell short of statistical significance. Still, the results “are the first proof” that using an antibody to precisely target a toxic chemotherapy dose into a solid tumor can work, said Kimberly Blackwell, a study author and professor of medicine at Duke University.
“It is fantastic data,” said Shanu Modi, a breast cancer oncologist at Memorial Sloan-Kettering Cancer Center in New York, who was not involved in the current trial. If approved, “it is going to be rapidly taken up by the oncology community. For sure, I will be using a lot of it.”
Roche, based in Basel, Switzerland, is in talks with the U.S. Food and Drug Administration and plans to file for marketing approval in the U.S. and Europe by the end of the year, said Sandra Horning, head of oncology research for Roche. A final review of survival data is due in 2014, she said.
The Swiss drugmaker used technology from ImmunoGen Inc. (IMGN:US), a Waltham, Massachusetts-based biotechnology company, to strap Herceptin together with a compound derived from a chemotherapy drug that proved too toxic for patients two decades ago. The combination delivers the powerful treatment straight to the tumor -- avoiding healthy cells and releasing its payload only once it gets to the cancer cells.
Cancer researchers have dreamed for decades of developing “smart bombs that can deliver cancer-killing agents directly to the tumor,” Blackwell said in the interview at the conference.
The study looked at women whose disease had progressed after previous treatment with Herceptin and chemotherapy. The experimental treatment delayed progression of the disease for 9.6 months, versus 6.4 months for the standard therapy. About 65 percent of patients who got T-DM1 were still alive after two years, compared with 47.5 percent of patients who got Tykerb and chemotherapy.
Modi and Blackwell predicted in interviews that a survival benefit will be proven with longer patient follow-up. Blackwell said the survival difference may turn out to be more than a year.
“The drug worked,” Blackwell, at Duke’s Durham, North Carolina campus, said in a statement. “It was significantly better than a very effective approved therapy.”
The data may be a “coming of age” for antibody-drug conjugates like T-DM1, Howard Liang, a Boston-based analyst for Leerink Swann & Co., wrote in a note to investors before the conference.
The study is “good news for women” because it shows T-DM1 can deliver a potent poison to cancer cells without many of the side effects suffered by the patients who got Tykerb, Roche’s Horning said. Diarrhea, vomiting and swollen, painful hands and feet were all less common in patients who took T-DM1.
“What we’re trying to do is deliver chemotherapy in a smarter way,” she said. “We feel like we’re moving to the next generation.”
Fewer toxic side-effects could be “a major selling point” for the T-DM1 drug, said Jennifer Litton, a breast cancer specialist at MD Anderson Cancer Center in Houston, who was not involved in the trial. “I have patients calling me asking for this drug.”
Roche is testing the armed antibody technology in eight molecules in early patient trials for prostate, ovarian, breast, non-Hodgkin’s lymphoma and other cancers, Stefan Frings, head of medical affairs oncology, said in a telephone interview. Also due for completion in 2014 is a trial combining T-DM1 with another new Roche breast cancer therapy, pertuzumab.
“This may really represent a transformational event in cancer therapies,” ImmunoGen Chief Executive Officer Dan Junius said in a telephone interview. Numerous antibody-drug conjugates like T-DM1 may be available within four years, he said.
The FDA rejected a request in 2010 to speed up the approval process for T-DM1 based on data from preliminary trials. It said that patients those trials had not exhausted all available options, said Charlotte Arnold, a Roche spokeswoman, in an e- mail.
About 1.4 million women are newly diagnosed with breast cancer every year and almost 460,000 die, making it the biggest cancer killer among women, according to the International Agency for Research on Cancer in Lyon, France.
About 25 percent of cases are distinguished by a protein called HER2 on the surface of the cancer cells that causes them to multiply more quickly. Herceptin latches onto HER2, blocking it without killing the cell.
Herceptin, approved in 1998 as one of the first targeted therapies against breast cancer, had 5.3 billion Swiss francs in sales last year, making it the drugmaker’s third-biggest-selling cancer drug after therapies Rituxan and Avastin.
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