The latest in cancer prevention, diagnosis & treatment
The Food and Drug Administration approved Halaven (eribulin) on Nov. 15 to treat metastatic breast cancer patients who have already tried at least two chemotherapy treatments.
Halaven is an injectable synthetic compound derived from the sea sponge Halichondria okadai. It’s a microtubule inhibitor that works by preventing cancer cells from dividing.
The decision comes after a phase 3 clinical trial found that Halaven extended median survival in patients with metastatic breast cancer who had already tried other treatments. Researchers presented the results of the trial at the annual meeting of the American Society of Clinical Oncology, stating that this is the first time a single agent has helped these previously treated patients live longer.
The study randomly assigned two-thirds of the 762 women to receive Halaven and the other one-third to receive a single-agent treatment chosen by their oncologist, with the control arm reflecting the real-life choices available to the women.
The patients receiving Halaven had a median overall survival of 13.1 months, compared with patients receiving another single-agent therapy, who had a median overall survival of 10.6 months. The most common side effects of Halaven are fatigue, nerve damage and a decrease in white blood cells. For more information, visit www.halaven.com or call 877-873-4724. —Lindsay Ray
Based on results of a phase 3 trial showing significantly improved overall survival, the Food and Drug Administration approved Herceptin (trastuzumab), a breast cancer drug, in combination with chemotherapy for use in patients with advanced HER2-positive gastric and gastroesophageal junction cancer who have not received prior treatment.
According to experts, this is the first positive trend in gastric cancer treatment in two decades, however, it only applies to the 22 percent of gastric cancers that overexpress HER2.
Researchers enrolled 594 patients for the international trial known as ToGA and randomized patients to receive Herceptin plus chemotherapy or chemotherapy alone. They found that patients in the Herceptin arm had a significantly improved overall survival rate compared with patients in the chemotherapy arm (13.5 months versus 11.1 months).
Side effects were similar in both treatment arms and included nausea (67 percent with Herceptin plus chemotherapy versus 63 percent with chemotherapy alone), vomiting (50 percent and 46 percent, respectively) and neutropenia (53 percent and 57 percent, respectively). For more information, visit www.herceptin.com or call 866-449-4372. —Lacey Meyer
Xgeva (denosumab) was given the green light on Nov. 18 for prevention of skeletal complications in patients with bone metastases from solid tumors, including breast and prostate cancers. The drug was originally approved this past June under the name Prolia for osteoporosis.
The FDA based its decision on several phase 3 studies that showed it reduced skeletal-related events (SREs), such as bone pain and fractures, better than the bisphosphonate Zometa (zoledronic acid) in patients with non-hematologic cancers that had spread to the bone. In one study, Xgeva delayed SREs in patients with prostate cancer by a median of 21 months compared with 17 months with Zometa. In patients with breast cancer, Zometa delayed SREs by a median of 26 months. Researchers are still waiting for a median time to SREs with Xgeva, meaning half of all patients in the experimental arm have yet to have a SREs.
Xgeva, a monoclonal antibody, works by blocking the RANK ligand protein from binding to its receptor on the surface of osteoclasts—cells that resorb bone tissue. By reducing osteoclast activity, Xgeva gives bone-building cells, called osteoblasts, more opportunity to build bone tissue—tipping the balance toward bone formation. Xgeva is not approved to prevent bone loss in patients with early-stage breast cancer or for patients on hormonal therapy, although it can be used under a different name, Prolia, in the case of osteoporosis. Also, while it is being studied in multiple myeloma, this recent approval does not include hematologic malignancies associated with SREs.
Side effects of Xgeva were similar to Zometa, including rare, but serious, instances of osteo-necrosis of the jaw, where in the bone tissue of the jaw bone dies, and low calcium levels in the blood, a condition called hypocalcemia. —Elizabeth Whittington
A novel androgen-blocking agent, abiraterone, has been shown to significantly improve overall survival by in men with metastatic castration-resistant prostate cancer who advanced on prior chemotherapy including Taxotere (docetaxel). The late-breaking results of the phase 3 study were presented in October at the annual meeting of the European Society of Medical Oncology in Milan.
The international trial randomly assigned 1,195 men to receive either abiraterone plus the steroid prednisone or placebo plus prednisone and found that treatment with abiraterone resulted in a median survival of 14.8 months compared with 10.9 months in the placebo arm. In addition to an increased survival of about four months, abiraterone also slowed time to disease progression—from 6.6 months to 10.2 months.
Prostate cancer growth is fueled by androgenic hormones, and while hormone therapy can slow growth for a period of time, most prostate cancers eventually become resistant to these treatments. Abiraterone counters the tumor’s ability to create growth-sustaining hormones by inhibiting production of androgen hormone in the testes, the adrenal glands and prostate cancer tumors themselves. About 38 percent of patients receiving abiraterone experienced a drop in PSA (prostate-specific antigen) of at least 50 percent from baseline compared to 10 percent on prednisone alone.
According to the study, abiraterone was well tolerated with side effects similar in the abiraterone and prednisone alone treatment arms including fluid retention (30.5 percent and 22.3 percent), low potassium levels (17.1 percent and 8.4 percent), liver function abnormalities (10.4 percent and 8.1 percent) and cardiac disorders (13.3 percent and 10.4 percent).
And while results are preliminary, they show abiraterone led to a 36 percent increase in median survival. Once a survival benefit of abiraterone was determined during a pre-specified interim analysis, the study was unblinded and patients in the placebo arm were allowed to cross over to receive the investigational drug. (For more information on abiraterone and other novel drugs to treat advanced prostate disease, see "Promise for Prostate.") —Lacey Meyer
A new “armed antibody” drug may offer hope for women with metastatic HER2-positive breast cancer, providing the same cancer-fighting properties of current treatments, but with fewer serious side effects.
Results of a large, phase 2 trial presented at the European Society for Medical Oncology annual congress show that the antibody drug conjugate trastuzumab-DM1 (T-DM1) slightly improves overall response rate with significantly fewer patients experiencing grade 3 or 4 adverse side effects—37 percent in the T-DM1 arm compared with 75 percent in the Herceptin (trastuzumab) plus Taxotere (docetaxel) arm.
Researchers followed 137 patients for a median of about six months, and patients in both treatment arms had a similar objective response rate with a 48 percent overall response in the T-DM1 arm and 41 percent in the control arm.
The first of a new class of cancer medicine called antibody-drug conjugates, T-DM1 consists of two existing cancer drugs to combine the anti-HER2 activity of Herceptin with antimicrotubule chemotherapy agent DM1 to deliver both drugs directly inside tumor cells and spare healthy cells.
The most common adverse events in both groups were nausea and fatigue. But incidence rates of serious adverse events were significantly higher in the Herceptin plus Taxotere arm compared to the T-DM1 arm, including hair loss (66.2 percent versus 1.5 percent), neutropenia (57.4 percent versus 7.5 percent) and diarrhea (45.6 percent versus 10.4 percent).
Other trials have shown efficacy of T-DM1 in previously treated metastatic HER2-positive breast cancer patients, but this is the first trial to evaluate the anti-HER2 drug conjugate as first-line therapy for patients with advanced breast cancer.
And with the encouraging phase 2 trial results, a larger phase 3 trial called MARIANNE is under way to evaluate taxanes Taxol (paclitaxel) or Taxotere plus Herceptin compared with T-DM1 and T-DM1 plus pertuzumab, a new investigational HER2-targeted therapy, as first-line treatment in HER2-positive metastatic breast cancer patients with no prior chemotherapy.
While these early results clearly show positive response rates, the researchers noted that final results of progression-free survival, one-year overall survival rates, and mature objective response rates from the phase 2 trial are expected in 2011. In July, the FDA rejected Roche’s request for accelerated approval of TDM-1 for women with advanced HER2-positive breast cancer based on the fact that there are other available therapies. —Lacey Meyer
The U.S. Food and Drug Administration announced Oct. 28 an additional approved indication for Sprycel (dasatinib) for the treatment of newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (chronic phase). Sprycel was first granted accelerated approval for Gleevec treatment resistant/intolerant disease in adults in 2006 and was granted to regular approval in 2009.
The most recent approval for Sprycel is based on results of an ongoing phase 3 study published in the New England Journal of Medicine in June. Sprycel achieved higher and faster response rates with 77 percent of patients reaching complete cytogenetic response in 12 months compared with only 66 percent of Gleevec (imatinib)-treated patients. The patients receiving Sprycel had a median time to confirmed complete cytogenetic response of 3.1 months compared with 5.6 months for patients receiving Gleevec. In addition, Sprycel had an improved median time to major molecular response with 6.3 months versus 9.2 months.
The most common, serious adverse events included anemia in 10 percent and 7 percent of patients, neutropenia in 21 and 20 percent of patients and thrombocytopenia in 19 percent and 10 percent of patients. Other all-grade reactions included fluid retention (19 percent versus 42 percent), nausea (8 percent versus 20 percent) and vomiting (5 percent vsersus 10 percent).
Sprycel is the third drug to be approved for first-line Philadelphia-positive CML—Gleevec in 2009 and Tasigna (nilotinib) in June 2010. —Lacey Meyer
An international phase 3 trial presented at the European Society of Medical Oncology annual meeting shows that adding Avastin (bevacizumab) to standard first-line chemotherapy for advanced ovarian cancer improves progression-free survival by almost two months.
The ICON-7 study randomized 1,528 patients—newly diagnosed with epithelial ovarian, primary or fallopian tube cancer after optimal surgery—to receive standard chemotherapy of Taxol (paclitaxel) plus carboplatin with or without Avastin. The Avastin arm resulted in an improved progression-free survival of 19 months compared to 17.3 months in the standard therapy arm.
This is the second study to show a possible benefit of Avastin in first-line ovarian cancer treatment—the Gynecologic Oncology Group (GOG)-218 trial published in June in the Journal of Clinical Oncology was the first. The GOG-218 trial was a three-arm study, comparing carboplatin and paclitaxel plus Avastin followed by placebo maintenance, carboplatin and paclitaxel plus Avastin followed by Avastin maintenance, and carboplatin and paclitaxel plus placebo followed by placebo maintenance. This trial also showed improved progression-free survival with the addition of Avastin (14.1 months) compared to carboplatin and paclitaxel alone (10.3 months).
Researchers reported that ICON-7 met its primary endpoint and demonstrated that at one year the risk of ovarian cancer progression was reduced by 15 percent.
A common side effect included hypertension, occurring in 25.9 percent of patients in the Avastin arm and 6.2 percent of patients in the control arm. Patients were followed for a median of 19.4 months. However, these are only preliminary results and don’t yet show improvement in overall survival, data researchers said won’t be mature for another two years. —Lacey Meyer