The gist: A new treatment that combines the drugs bortezomib and fulvestrant has shown promise in treating post-menopausal women with metastatic hormone receptor-positive breast cancer whose disease worsened after being treated with drugs called aromatase inhibitors. The combo treatment was tested in 118 patients in a clinical trial. It doubled the number of patients still alive after 12 months, and it lowered the chance of patients’ cancer worsening. Further studies will continue to measure the effectiveness of the treatment.
“A new combination of cancer drugs delayed disease progression for patients with hormone-receptor-positive metastatic breast cancer, according to a multi-center phase II trial. The findings of the randomized study (S6-03) were presented at the 2014 San Antonio Breast Cancer Symposium, held Dec. 6-9, by Kerin Adelson, M.D., assistant professor of medical oncology at Yale Cancer Center and chief quality officer at Smilow Cancer Hospital at Yale-New Haven.
“The trial enrolled 118 post-menopausal women with metastatic hormone-receptor-positive breast cancer whose cancer continued to progress after being treated with an aromatase inhibitor. The study, based on work done by Doris Germain of Mt. Sinai Hospital, found that the combination of the drugs bortezomib and fulvestrant—versus fulvestrant alone—doubled the rate of survival at 12 months and reduced the chance of cancer progression overall.
“Bortezomib, used most commonly in treating multiple myeloma, is a proteasome inhibitor that prevents cancer cells from clearing toxic material. Fulvestrant causes clumping of the estrogen-receptor protein. When bortezomib blocks the ability of the cell to clear these protein clumps, they grow larger and become toxic to the cancer cells. This, in turn, amplifies the effectiveness of fulvestrant, a drug commonly used in this subset of patients.
“The drug combination doubled the number of patients whose cancer had not progressed after one year from 14% to 28%, according to Adelson.”
Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test the effectiveness of a mantle cell lymphoma treatment that combines the drugs bortezomib (Velcade) and lenalidomide (Revlimid). Specifically, the trial tested the treatment for patients whose cancer did not get better after previous treatments or whose cancer returned after treatment. The results of the clinical trial were “disappointing.” The combination treatment was less effective than either drug on its own.
“Although the majority of patients with mantle cell lymphoma respond to initial therapy, the duration of remission is typically short (1.5 to 3 years). Although bortezomib (Velcade) and lenalidomide (Revlimid) as single agents have been associated with response rates as high as 53% in patients with relapsed/refractory disease, Morrison et al reported an overall response rate of almost 40% with combination bortezomib/lenalidomide therapy in an article published in Leukemia & Lymphoma.
“The incidence of mantle cell lymphoma has increased dramatically over the past several decades. The median overall survival is 3 to 6 years with standard chemotherapy approaches, and fewer than 15% of patients are long-term survivors.
“Therefore, researchers continue to investigate newer therapeutic options for these patients. One such approach was the combination of bortezomib and lenalidomide, particularly in patients who experienced relapse from or were refractory to previous treatments. In the phase II CALGB 50501 trial, a team of investigators from the University of Minnesota, Duke University, Dana-Farber Cancer Institute, Ohio State University, Washington University, and Georgetown University attempted to evaluate the feasibility of combination treatment with bortezomib and lenalidomide in patients with relapsed or refractory mantle cell lymphoma.”
“In a modest-sized lab at the Moores Cancer Center at the University of California, San Diego, scientists investigating how cancer cells develop resistance to drug treatments recently discovered something that surprised even the most seasoned members of the research team: A new generation of drugs that are currently among the most popular treatments for lung, breast and pancreatic cancers actually induce drug resistance and spur tumor growth.
“These popular cancer drugs, known as receptor tyrosine kinase inhibitors (RTKs), are actually making cancers stronger. That’s the bad news. The good news is that researchers believe they have found a way to eliminate that threat.
“Researchers found that two of the drugs — Erlotinib for lung cancer and Lapatinib for breast cancer — are effective for a while, but eventually stop killing cancer cells and begin prompting them to resist the drug and become more aggressive.
“ ‘We knew that cancer typically builds up a resistance to these and other drugs. But we did not know that these drugs actually induce tumor progression,’ said David Cheresh, Moores’ vice chair of pathology and the lead researcher on this study.”
Image: A breast cancer cell. London Research Institute EM Unit/Cancer Research UK
“Some drug-resistant cancers of the lung, pancreas and breast might be made vulnerable again by treating them with a medication already approved for another type of cancer, according to a new study led by scientists at UC San Diego.
“Researchers at UCSD Moores Cancer Center said they plan to start a clinical trial to test the use of Velcade for lung cancer in about six months. This quick start is possible because the drug is currently on the market, said Dr. Hatim Husain, an author of the study who is designing the clinical trial. For more information about the trial, call (858) 822-5182.”
Editor’s note: Clinical trials can be important treatment options for some patients. This one might be particularly appropriate for people who have taken the drug Tarceva (erlotinib) but became resistant to it. The drug combination being tested in this clinical trial has previously shown disappointing results, but the researchers are hopeful that by using molecular testing to identify patients who are more likely to benefit, they may be able to successfully use the treatment. Learn more about clinical trials here.
An analysis of multiple clinical trials compared erlotinib (Tarceva) alone to combining Tarceva with other targeted therapies as second-line treatment for advanced non-small cell lung cancer (NSCLC). In the various trials, Tarceva was combined with bevacizumab (Avastin), bortezomib (Velcade), everolismus (Afinitor), sorafenib (Nexavar), sunitinib (Sutent), entinostat, tivantinib, and R1507. While combined therapy produced more side effects, it was more effective than Tarceva alone. Notably, the trials included many patients who had not been tested for mutations in the EGFR and KRAS genes. In patients who had EGFR mutations and/or lacked KRAS mutations, Tarceva alone tended to control cancer progression better than combined therapy, highlighting the importance of biomarker testing to identify which patients are most likely to benefit from different therapies.