By Michelle Fay Cortez
Dec. 8 (Bloomberg) — Drugs from Roche Holding AG and Novartis AG that target different molecular drivers of breast cancer slowed tumor progression in separate studies that doctors say will change the way they care for patients.
Research released yesterday at the San Antonio Breast Cancer Symposium should alter the care of 80 percent of women with advanced tumors, said Jose Baselga, chief of oncology at Massachusetts General Hospital. Breast cancer is diagnosed in more than 230,000 women in the U.S. each year, making it the most common tumor type, and kills almost 40,000.
Roche’s experimental drug pertuzumab delayed progression of metastatic cancer fueled by the HER2 protein for an extra 6.1 months when it was added to standard treatment with the company’s Herceptin and chemotherapy. Novartis’ Afinitor, approved for kidney and pancreatic cancer, slowed progression an additional 4.2 months when added to hormone treatment in women with treatment-resistant tumors driven by estrogen.
“These are two new therapies, targeted therapies, that will change the standard of care for women with metastatic disease,” Baselga, the lead author of both studies, said in a telephone interview. “They are elegant, they are hypothesis- driven and they are working through well-known mechanisms.”
The studies were funded by Roche and Novartis, both based in Basel, Switzerland. The results were simultaneously published in the New England Journal of Medicine. Roche requested U.S. approval of pertuzumab based on the findings this week and Novartis plans to file for expanded clearance for Afinitor by the end of the year.
About 25 percent of breast cancers are driven by HER2, a protein that tells malignant cells to grow and spread throughout the body. Roche’s Herceptin, the first medicine approved to directly target HER2 positive cancers, blocks its receptors on the outside of the cell. Pertuzumab stops the protein from joining with HER3 and squelching an even stronger growth signal.
Afinitor was given to women with tumors fueled by estrogen, rather than HER2. While estrogen-blocking treatment is used first, the cancer sometimes resumes growing. Afinitor blocks a different pathway, known as mTor, that spurs the growth.
“We’re beginning to see the promise of looking at tumors on the molecular level,” said Jennifer Litton, an oncologist at the University of Texas’s MD Anderson Cancer Center in Houston, in an interview. “Now that we have the ability and it’s financially reasonable, we are dissecting the tumors’ molecular weaknesses and targeting them with smart bombs, and we’re beginning to see improved outcomes as a result.”
Treating the right patients even earlier with the targeted “smart drugs” may cure more women or make metastatic breast cancer a chronic and controllable disease, she said. Currently, breast cancer is considered incurable once it has spread, and treatment is designed to prolong survival.
Neither drug has yet to show longer survival for women with metastatic breast cancer, though the early results appear promising, particularly for pertuzumab, the researchers said.
“These progression-free survival data for pertuzumab are clearly a measure of a direct treatment effect,” said Sandra Horning, Roche’s head of global oncology development, in a telephone interview. “We believe the magnitude is clinically meaningful.”
Roche’s application with the U.S. Food and Drug Administration is strong, with evidence the drug benefits women at different stages, she said. It also has a positive safety profile, with little increased risk of serious side effects when the drug was added to other treatments, she said.
One of the biggest drawbacks for combining cancer drugs is the expense, doctors said. Novartis’ Afinitor costs $6,500 to $7,000 for a 28-day supply. Roche’s Genentech unit sells Herceptin for $4,500 a month. The company hasn’t set a price for pertuzumab, Krysta Pellegrino, a spokeswoman, said in an e-mail.
“The main issue for the world is cost,” said Edith Perez, deputy director of the Mayo Clinic’s cancer center in Jacksonville, Florida, in an interview. “I hope pertuzumab is priced at a level that would allow prompt incorporation into the treatment regimen so patients can benefit.”
The FDA last month revoked approval of Roche’s Avastin for metastatic breast cancer after studies failed to prove it lengthened life. The medicine, with $6.2 billion in 2010 sales, was initially shown to slow the worsening of breast cancer. The benefit didn’t translate into longer life and the drug had serious side effects, the FDA said.
A third study presented at the meeting showed adding Avastin to Herceptin and chemotherapy for women with recurring HER2 positive tumors didn’t significantly delay progression of the disease. Additional work is under way to determine what genetic factors in a tumor may make it most susceptible to Avastin, the researchers said.
The pertuzumab study, dubbed Cleopatra, shows using two drugs to block HER2 are better than one, said Harold Burstein, a breast oncologist at Dana-Farber Cancer Institute in Boston. The cancer resumed growing after 18.5 months in women getting all three drugs, compared with 12.4 months for those who didn’t get pertuzumab in the study involving 808 patients.
“It’s great to see such a dramatic improvement in progression free survival with hardly any toxicity, and an emerging signal of a survival advantage,” Burstein said in an interview. “Everyone expects FDA will approve pertuzumab on this data and it will become a widely used treatment option.”
The Novartis study known as Bolero-2 found breast tumors resumed growing after an average of 7.4 months for those given Afinitor plus Pfizer Inc.’s Aromasin, compared with 3.2 months for women on Aromasin alone. All of the women had previously seen their disease worsen while they were taking other drugs to blunt hormones that signal the cancerous cells to grow.
The study was originally halted in July because of the benefit and an earlier analysis was presented at a European cancer conference in September. Women getting Afinitor had more side effects, including sores in the mouth that can make it hard to eat and problems with lung function.
“In spite of the toxicity, this is the first time that we see such a degree of delay of tumor progression in women with refractory estrogen receptor positive breast cancer,” said Mayo Clinic’s Perez, who served as head of the independent panel monitoring the trial. “This should serve as a guide to change standards of care.”