Significant survival benefit observed in women with HER2 negative breast cancer
Data from a pooled analysis presented recently at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) provides further evidence that Halaven (eribulin) improves overall survival (OS) in women with advanced breast cancer compared with other
standard therapies.
In particular, a significant OS benefit was observed in women with human epidermal growth-factor receptor-2 (HER2) negative breast cancer, a subtype that affects an estimated 85% of women with breast cancer.
This OS benefit was also seen in people with triple negative breast cancer (TNBC), but not in women with HER2 positive breast cancer. There were no noticeable differences in the tolerability and safety data previously shown in the EMBRACE and 301 studies.
Dr Chris Twelves, Professor of Clinical Cancer Pharmacology and Oncology and Honorary Consultant in Medical Oncology at the University of Leeds and St James’s Institute of Oncology, said: “Eribulin remains the only single agent chemotherapy proven to improve significantly overall survival in women with advanced breast cancer after either adjuvant or metastatic anthracycline and taxane treatment. These new data clearly confirm that women with advanced breast cancer benefit from eribulin. The overall survival benefit that was observed in HER2 negative and triple negative breast cancer patients is particularly interesting as very often these patients are underserved with few effective treatment options.”
The pooled analysis examined data from two pivotal Phase III studies of more than 1,800 women; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician’s Choice Versus Eribulin) and study 301. The objective of the analysis, requested by the European Medicines Agency (EMA), was to assess OS in the overall intent to treat (ITT) population and in subgroups based on HER2 and hormone receptor status.
Eribulin is a non-taxane, microtubule dynamics inhibitor currently indicated for the treatment of people with breast cancer who have previously received at least two chemotherapeutic regimens for metastatic disease and whose prior therapy should have included an anthracycline and a taxane. Eribulin belongs to a class of antineoplastic agents, the halichondrins, which are natural products, isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division.
HER2 is a protein that is found on the surface of cells. In HER2-positive breast cancer there is more (over expression) of this protein found on the surface of tumour cells compared with normal breast cells. This protein can be targeted with HER2 targeted therapies such as Herceptin, in people who overexpress HER2, but not in people with normal levels of HER2 protein (HER2-negative) breast cancer. Breast cancers are routinely tested for the presence of HER2 to decide the most appropriate treatment. Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express the genes for oestrogen receptor, progesterone receptor and HER2.

RESONATE study indicates ibrutinib yields lasting tumour responses
Early findings from the phase III RESONATE study, presented at ASCO, indicate that ibrutinib yields lasting tumor responses and marked improvement in survival over standard ofatumumab for patients with relapsed chronic lymphocytic leukemia (CLL). This is the first time an oral drug has demonstrated a survival improvement over standard therapy in relapsed CLL. Just as important, the therapy was well tolerated by patients, causing few serious side effects.
CLL is the most common form of leukemia in adults. The standard treatment for CLL is chemo-immunotherapy, a combination of intensive chemotherapy and an antibody such as rituximab. However, elderly patients, who account for the majority of patients with CLL, often cannot tolerate intensive chemotherapy. Ofatumumab is an alternative option for such patients, but studies have shown it is much less effective than intensive chemotherapy.
Lead study author John Byrd, MD, a professor of medicine at The Ohio State University Comprehensive Cancer Center in Columbus, Ohio, said: “With ibrutinib, about 80% of patients were still in remission at one year, twice as many as we would expect with standard therapy. Although the follow-up was short in this study, the data definitely support the use of ibrutinib before anything else in this setting.”
Ibrutinib was FDA approved for the treatment of CLL in February of this year, through the FDA’s accelerated review process, less than five years after entering phase I clinical trials.
In the study, 391 patients with relapsed or refractory CLL or small lymphocytic lymphoma (a subtype of CLL) that had progressed after two or more prior therapies were randomly assigned to treatment with ofatumumab or ibrutinib. The median patient age was 67 years, and 40% were older than 70 years.
At a median follow-up of 9.4 months, the response rates were dramatically higher in the ibrutinib arm compared to the ofatumumab arm (42% versus 4%). An additional 20% of patients treated with ibrutinib had a partial response with persistent lymphocytosis (increase in white blood cells called lymphocytes). Ibrutinib was associated with an 80% lower risk of disease progression and a 57% lower risk of dying compared to ofatumumab; the median progression-free and overall survival have not been reached. Ibrutinib had similarly high activity in two very high-risk groups of patients (17p deletions and purine analog refractory).
Based on these striking early results, patients in the ofatumumab arm were offered the opportunity to cross over to the ibrutinib arm, and patient follow-up continues. According to the researchers, the median overall survival is expected to be in the range of several years.
Overall, both ibrutinib and ofatumumab were well tolerated. Diarrhoea, minor bleeding, and atrial fibrillation were more common in the ibrutinib arm, whereas peripheral neuropathy was more common in the ofatumumab arm. This study alleviated concerns about kidney problems that were raised in the phase II ibrutinib study.
This research was supported by Pharmacyclics. “This phase III study in relapsed refractory chronic lymphocytic leukemia confirms that ibrutinib, administered orally, has significant efficacy and is well-tolerated,” said Olatoyosi Odenike, MD, ASCO Expert. “These results provide a compelling new treatment option for patients with chronic lymphocytic leukemia, including older adults with this disease, and will significantly change practice.”

SELECT study shows lenvatinib is effective against thyroid cancer
Findings from the SELECT phase III study were presented at ASCO and show that lenvatinib is highly effective against differentiated thyroid cancer that is resistant to standard radioiodine (RAI) therapy. The new oral targeted drug delayed disease progression by 14.7 months, and nearly two-thirds of patients experienced tumor shrinkage. The median overall survival has not been reached.
Differentiated thyroid cancer is the most common subtype of thyroid cancer, accounting for about 85% of the 60,000 thyroid cancer cases diagnosed each year in the US. Although differentiated thyroid cancer is generally curable with standard treatment—surgery and RAI—roughly 5–15% of patients develop RAI resistance. Another targeted drug called sorafenib was approved by the FDA in November 2013 to treat this same population of patients.
Lenvatinib is an oral tyrosine kinase inhibitor that blocks several targets in a cancer cell, including VEGFR1-3, FGFR 1-4, PDGFR-β, KIT, and RET. It is being explored in phase II and phase III clinical trials as a potential treatment for liver, lung, and kidney cancers and other types of solid tumors.
In this study, 392 patients with advanced, RAI-resistant, differentiated thyroid cancer that had progressed within a year were randomly assigned to treatment with either lenvatinib or placebo. Patients on the placebo arm were allowed to cross over to the lenvatinib arm upon disease progression.
Approximately 65% of patients experienced tumor shrinkage in the lenvatinib arm, compared to only 3% in the placebo arm. The majority of responses occurred within two months of starting treatment. The median progression-free survival was 18.3 months in the lenvatinib arm versus 3.6 months in the placebo arm. The median overall survival has not been reached.
This research was supported by Eisai Inc.
Lead study author Martin Schlumberger, MD, a professor of oncology at the University Paris Sud in Paris, France, said: “We are confident that, based on our findings, lenvatinib will eventually become a standard treatment for radioiodine-resistant thyroid cancer. As little as a year ago, this group of patients had no effective treatment options. It’s remarkable that we now have two active drugs in this setting, both of them tyrosine kinase inhibitors.”

New targeted drug for recurrent ovarian cancer
Findings from a federally funded, NCI-sponsored phase II study also presented at ASCO suggest that the combination of two investigational oral drugs, the PARP inhibitor olaparib and the anti-angiogenesis drug cediranib, is significantly more active against recurrent, platinum chemotherapy-sensitive disease or ovarian cancer related to mutations in BRCA genes
than olaparib alone. The progression-free survival was 17.7 months with the combination treatment versus nine months with olaparib alone.
“The significant activity that we saw with the combination suggests that this could potentially be an effective alternative to standard chemotherapy,” said lead study author Joyce Liu, MD, MPH, an instructor in medical oncology at Dana-Farber Cancer Institute in Boston, MA.
This study is the first time a combination of a PARP inhibitor and an anti-angiogenic drug has ever been explored in a clinical trial for ovarian cancer.
PARP is an enzyme involved in many functions in a cell, including repair of DNA damage. Inhibition of PARP may cause cancer cells to die. Anti-angiogenic drugs block the growth of blood vessels in the tumor. It confirms preclinical research which suggested that olaparib and cediranib synergize, meaning they work together to make each other more active.
Dr Liu and her colleagues designed this trial to confirm, in a clinical setting, that the combination of these two drugs was more active than the single drug olaparib alone.
As many as 80% of women with high-grade serous ovarian cancer experience a relapse after initially responding to chemotherapy. When the cancer comes back, it is more difficult to treat, because it will have spread to the pelvis and abdomen, or even the lungs. The current standard treatment for recurrent ovarian cancer is chemotherapy, which often causes significant side effects. Even in the setting of initial response, resistance to chemotherapy eventually develops. Therefore, researchers have been exploring alternate regimens using targeted drugs, with the goal of overcoming such treatment resistance.
Ninety women with recurrent, platinum-sensitive (disease that responds to treatment with platinum-based chemotherapy), high-grade serous or BRCA mutation-related ovarian cancer, were randomly assigned to treatment with olaparib alone or olaparib plus cediranib. The women had no prior treatment with anti-angiogenic drugs in the setting of recurrent ovarian cancer or PARP inhibitors.
Tumor shrinkage rates were markedly higher in the combination arm than in the olaparib arm (80 versus 48%). Five patients in the combination arm and two patients in the olaparib alone arm had a complete remission.
The combination treatment substantially delayed disease progression, with a progression-free survival of 17.7 months compared to nine months for olaparib alone. Past trials of standard chemotherapy in the platinum-sensitive setting have demonstrated progression-free survival times between eight and 13 months.
This study was supported by the National Cancer Institute, National Institutes of Health.