ASCO 2010: The Roundup

2 Jul 2010

By freelance medical journalist Rhonda Siddall

The 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) was held in Chicago, from June 4 to June 8, 2010. This year's Annual Meeting focused on Advancing Quality through Innovation. More than 30,000 cancer specialists from around the world gathered at the meeting to discuss the latest innovations in research, quality, practice and technology in cancer. This meeting was a platform for the release of around 4,000 scientific abstracts and highly anticipated research news. ASCO is the largest gathering of cancer specialists in the world, and always generates extensive media coverage. This year's ASCO revealed some exciting results from clinical trials of new treatment approaches, particularly in the treatment of advanced melanoma, prostate cancer and advanced breast cancer, as well as setting out new challenges for managing cancer in clinical practice. Here is the pick of ASCO 2010.

An investigational drug multitargeted kinase inhibitor called vandetanib can slow down the rate that medullary thyroid carcinoma progresses by more than 50%, according to results presented at ASCO from the largest-ever clinical trial of treatment for this type of cancer. The results came from a study of 311 patients with locally advanced or metastatic thyroid cancer sponsored by the National Cancer Institute (NCI) in the US. Presenting the results, Dr Samuel Wells from the NCI, told the meeting that patients treated with vandetanib had a progression rate of 32% compared with a 51% progression rate for patients who took the placebo. Vandetanib works by inhibiting tumour angiogenesis and tumour-cell proliferation by targeting RET, vascular endothelial growth factor (VEGF) receptor and epidermal growth factor receptor (EGFR). The most common side effects that occurred more often with vandetanib than placebo were: diarrhoea (56% versus 26%), rash (45% versus 11%), nausea (33% versus 16%), and hypertension (32% versus 5%). Four times as many patients on vandetanib stopped taking the drug because of side effects compared to placebo-treated patients.

Dr Wells said that the results were of interest because treatment with vandetanib could improve progression-free survival for people who had a stage of the disease for which there is currently no effective treatment.

A monoclonal antibody, denosumab, appears to significantly increase the time before a patient with prostate cancer experiences a bone-related event such as a fracture, researchers said at ASCO. Results presented from a trial by Dr Karim Fizazi from the Institut Gustave Roussy in France showed that on average, a patient with prostate cancer experienced a fracture ten months earlier if they were treated with zoledronic acid rather than denosumab. Dr Fizazi told the meeting: "Denosumab was superior to zoledronic acid in preventing or delaying the first skeletal-related events and in preventing or delaying multiple skeletal events." The trial enrolled 945 patients who were treated with zoledronic acid 4 mg administered intravenously, and 943 patients who took subcutaneous denosumab 120 mg. The people in the trial had prostate cancer that was not receptive to hormone therapy and they also had bone metastases. About a fifth of patients in the trial had skeletal-related events that required radiation to the bone to relieve pain and 15% of patients had pathological bone fractures. Commenting on the trial's findings, Dr Robert Coleman from the University of Sheffield said that "some skeletal-related events are not of equal concern to patients", adding that this issue needed to be balanced with adverse events due to treatment and the potential for life-long treatment.

An experimental monoclonal antibody called ipilimumab helps patients with advanced, previously treated melanoma live longer, according to results from the first trial of a treatment to ever show an overall survival benefit in metastatic melanoma.
Ipilimumab helped patients with metastatic melanoma live 34% times longer than those who received a vaccine called gp100. Patients in the trial who received ipilimumab survived, on average, 10.1 months compared with an average of 6.4 months for those people who got the vaccine. Lead investigator Dr Steven O'Day from the Angeles Clinic and Research Institute in Los Angeles, said: "Over the last 30 years, randomised clinical trials have repeatedly failed to demonstrate an improvement in overall survival in patients with advanced melanoma. It's an extremely difficult disease to treat so these results are an exciting advance for patients." The results from this trial were presented at ASCO and published simultaneously online in the New England Journal of Medicine. Ipilimumab is given intravenously and it works by activating the immune's systems T-cells, which seek and destroy melanoma cells. The researchers reported that ipilimumab was generally well tolerated, but between 10 and 14% of ipilimumab patients experienced sometimes severe side effects such as rash and inflammation of the colon compared to just 3% of patients on the vaccine.

A novel chemotherapy drug called eribulin improves survival in women with advanced breast cancer who have already had a lot of chemotherapy, researchers reported at ASCO. Christopher Twelves from the University of Leeds and St. James' University Hospital in the UK said that women with advanced breast cancer who took eribulin survived, on average, 13.12 months compared with an average survival of 10.7 months for those women who were treated with either another chemotherapy drug, a biologic drug or endocrine therapy, according to their doctors' recommendation. Professor Twelves said: "These are promising results for women who have already received all of the recognised treatments. Up until now, there hasn't been a standard treatment for women with such advanced breast cancer." Over the past 25 years, only a handful of drugs of any type have been shown to improve overall survival in metastatic breast cancer, added Professor Twelves. Eribulin mesylate is a new type of "microtubule dynamics inhibitor" that affects cell division and the drug is derived from a marine sponge. The international, multicenter trial, EMBRACE, is the first to compare eribulin mesylate to "treatment of physician's choice" in women with locally recurrent or metastatic breast cancer who had already received an average of four prior chemotherapy drugs such as anthracyclines or taxanes. This comparison was chosen because no single chemotherapy regimen is currently standard. Professor Twelves and his colleagues compared overall survival among 762 patients with metastatic breast cancer who were randomized to receive either eribulin or their physician's choice of therapy, which was almost always another chemotherapy. The study's secondary endpoints (progression-free survival and objective response rate) also favoured eribulin, which Professor Twelves said was generally well tolerated. He concluded: " This trial is significant because the era of targeted biological therapies had led us to assume that advances in patient care were not likely to come from innovations in chemotherapy. Results from EMBRACE prove that this assumption was incorrect."

The investigational taxane cabazitaxel extends survival among hormone-refractory prostate cancer patients whose cancers have progressed despite treatment with docetaxel, researchers reported at ASCO. A multinational phase III study, the TROPIC study, conducted among 755 men, found that mortality risk was reduced by 28% with cabazitaxel compared with mitoxantrone. Dr Johann De Bono from the Royal Marsden Hospital in London told the meeting: "Cabazitaxel is the first treatment to show a survival benefit to patients with metastatic castrate-resistant prostate cancer after failure of docetaxel-based therapy." The trial randomized advanced prostate cancer patients to receive cabazitaxel or mitoxantrone and all patients received prednisone. On average, patients survived 15.1 months on cabazitaxel compared to 12.7 months on mitoxantrone. Patients receiving cabazitaxel experienced more grade 3 or higher neutropenia than mitoxantrone-treated patients. In a separate study, results showed that men with advanced prostate cancer lived significantly longer when treated with radiation and hormonal therapy compared with hormonal therapy alone. Adding radiation therapy to androgen deprivation therapy (hormone therapy) reduced the risk of dying from prostate cancer by 43% in men with locally advanced prostate cancer compared to hormone therapy alone.

Adding the targeted agent bevacizumab to initial chemotherapy treatment significantly reduced the risk of relapse in women with advanced ovarian cancers and other related cancers, results presented at ASCO showed. Maintenance therapy with bevacizumab after standard chemotherapy decreased the risk of progression by 28% compared with chemotherapy alone. Researchers said that this approach should now be considered "one standard option" for women with advanced ovarian cancer or fallopian tube cancer and that this is the first time an anti-angiogenic agent has been shown to improve progression-free survival in this type of cancer.

The results come from an international study that included 1,873 women with newly diagnosed stage III or IV ovarian, primary peritoneal or fallopian tube cancer who had already undergone surgery. The researchers found that women who received standard chemotherapy plus bevacizumab followed by up to 10 months of bevacizumab maintenance therapy had a longer period of progression-free survival (average of 14.1 months) compared to an average of 10.3 months for women who received standard chemotherapy only. Adverse events were similar in the treatment groups. In another study, women who have ovarian cancer that has become chemotherapy-resistant ovarian cancer in genetically vulnerable women appeared to regain its sensitivity after treatment with the PARP inhibitor olaparib. Among a group of 26 ovarian cancer patients who had become resistant to a taxane or carboplatin drug, more than half responded again to the chemotherapy after progression on olaparib. Of the patients, 25 had BRCA mutations and one had a strong family history of BRCA-related breast cancer. All had received multiple prior chemotherapy regimens.

Removing additional axillary lymph nodes to look for more breast cancer cells in women with limited disease spread in the sentinel node does not improve survival, suggesting that there is no benefit to removing more lymph nodes than the sentinel node only, according to a new trial presented at ASCO. A randomized clinical trial involving more than 800 women found that performing axillary lymph node dissection in early-stage breast cancer patients whose sentinel node showed evidence of cancer spread had no impact on the risk of dying of the disease. Another presented at the meeting showed that node removal does not improve outcomes for women with node-negative disease.

A single dose of radiation delivered at the same time as surgery may work as well as several weeks of external beam radiation, according to results presented at the meeting and published simultaneously in a fast-tracked paper in the Lancet. In the TARGIT-A trial, whole breast external beam radiotherapy was compared with single-dose targeted intra-operative radiotherapy after breast conserving surgery in more than 2,000 women under the age of 45 with invasive ductal carcinoma. After four years of follow-up, there were six local recurrences in the TARGIT group and five in the external beam group, the researchers said. Professor Michael Baum, professor emeritus of surgery at the University College London and chair of the TARGIT trial said: "It is the sincere hope of the TARGIT group that these results influence a paradigm shift from conventional radiation approaches to single-dose treatment for eligible patients."

Maintenance therapy with lenalidomide after autologous stem-cell transplant (ASCT) slowed disease progression by 54% after three years compared with placebo in patients with multiple myeloma, according to results presented at the meeting. "These results are very promising and if confirmed in a final analysis suggests that maintenance therapy with lenalidomide can improve quality of life in patients with myeloma by delaying the need for more intensive therapy to treat a relapse, said Michael Attal, who was the lead author of the study and is from Purpan Hospital in Toulouse, France. Lenalidomide is a small molecule analogue of thalidomide. Following stratification according to response to transplant, beta-2 microglobulin and chromosome 13 deletions, 614 patients were given two months of oral lenalidomide consolidation therapy at 25 mg a day orally then randomized to placebo or lenalidomide until relapse occurred. Progression-free survival was 34% at three years in the placebo arm and 68% in the lenalidomide arm. This benefit was observed whether or not patients had achieved a complete response after ASCT. Dr Attal said that maintenance lenalidomide was well tolerated.

Dasatinib was superior to the standard first-line drug, imatinib, in treating patients newly diagnosed with chronic myeloid leukaemia (CML), according to the results of a phase III trial presented at the meeting. Professor Hagop Kantarjian from the University of Texas who led the study said that the findings suggest dasatinib should be used upfront in patients newly diagnosed with CML. In the study, the complete cytogenetic response (CCyR) was compared and after a year, the rate of confirmed CCyR was significantly higher among patients who received dasatinib than imatinib. The rate of major molecular responses was also higher in the dasatinib group, another indication of the drug's relatively superior effectiveness. Both drugs, according to Professor Kantarjian, were generally well tolerated.