No Benefit to Afatinib in HER2-Positive Breast Cancer With Brain Metastases

“The use of afatinib or afatinib plus vinorelbine during or after treatment with trastuzumab, lapatinib, or both failed to show a patient benefit in women with HER2-positive breast cancer with progressive brain metastases compared with investigator’s choice of treatment, according to the results of a phase II study published in Lancet Oncology.

“Afatinib, an oral inhibitor of the ErbB family of proteins, did benefit about one-third of patients assigned to the treatment, but had no better activity than investigator’s choice of therapy, which consisted mostly of trastuzumab or lapatinib plus chemotherapy.

“ ‘No objective responses were achieved in patients treated with afatinib alone, but around one-third of patients, including those treated with afatinib alone, did not have disease progression during the first 12 weeks,’ wrote researcher Javier Cortés, MD, of Vall d’Hebron Institute of Oncology in Barcelona, and colleagues. ‘No further development of afatinib for HER2-positive breast cancer is currently planned.’ “

Prognostic Factors Identified in Patients With ALK‑Rearranged NSCLC and Brain Metastasis

“In a study reported in the Journal of Clinical Oncology, Johung and colleagues identified factors that distinguished survival rates among patients with ALK-rearranged non–small cell lung cancer (NSCLC) and brain metastasis.

“The study included 90 patients from six institutions. Of them, 84 patients had received radiotherapy to the brain, consisting of stereotactic radiosurgery or whole-brain radiotherapy, and 86 patients had received tyrosine kinase inhibitor therapy (crizotinib [Xalkori] in 84 and a second-generation tyrosine kinase inhibitor in 41).”

Rare Mutation May Extend Survival in Lung Cancer Patients with Brain Metastases

“Most patients with non-small cell lung cancer (NSCLC) that has metastasized to the brain have a dire prognosis. But Yale researchers have identified a subset of those patients with a rare genetic mutation who are living significantly longer than patients without the mutation.

“The findings were published this month in the Journal of Clinical Oncology and will be presented Monday, Oct. 19 at the 2015 Annual Meeting of the American Society for Radiation Oncology.

“NSCLC accounts for 85% of all lung cancers, with 30%-50% of patients developing metastatic disease to the brain. Typically, patients with this diagnosis die of the disease within seven months. However, patients with the rare ALK mutation, which is found in just 5% of NSCLC cases, are living an average of four years, with the disease controlled in the brain nearly a year after their initial treatment, said the study’s lead author Kimberly Johung, M.D., assistant professor of therapeutic radiology.”

Melanoma Brain Metastases: Q&A With Keith Black, MD

“Malignant melanoma is one of the most common primary tumors to spread to the brain. In close to 50% of patients who have metastatic melanoma, the disease can be found in their brain.

“For example, in former President Carter’s case, the cancer was first found in his liver and later removed. During his press briefing last month, he announced that the melanoma had metastasized to his brain, and he was beginning treatment with pembrolizumab immediately.

“In order to learn more about melanoma metastases to the brain, Targeted Oncology interviewed Keith Black, MD, chairman and professor, Department of Neurosurgery, Cedars-Sinai Medical Center, director, Maxine Dunitz Neurosurgical Institute, director, Johnnie L. Cochran, Jr, Brain Tumor Center, and Ruth and Lawrence Harvey Chair in Neuroscience.”

Anti-HER2 Therapy After WBRT Increases Survival in Brain Mets Patients

“Both chemotherapy and anti–human epidermal growth factor receptor 2 (HER2) therapy can improve survival outcomes in HER2-positive breast cancer patients with brain metastases who undergo whole-brain radiotherapy (WBRT), according to a new retrospective study.

“ ‘The incidence of brain metastases is higher in HER2-positive breast cancer compared with other breast cancer patients,’ wrote study authors led by Jiayi Chen, MD, of Shanghai Cancer Center at Fudan University in China. ‘Although adjuvant trastuzumab could not effectively prevent brain metastases, recent studies demonstrated a significant survival benefit of salvage trastuzumab-based therapy for these patients.’

“In the study, the authors retrospectively analyzed 60 patients with HER2-positive breast cancer and brain metastases who underwent WBRT to examine the benefits of various systemic therapies in this setting. The results were published in Breast Cancer.”

ONT-380 Has Stage IV HER2+ Breast Cancer Patient 'Worrying About Normal Stuff Again'

“Promising clinical trial results presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2015 show activity of the investigational anti-cancer agent ONT-380 against HER2+ breast cancer, in one case specifically against brain metastases and in another case in overall survival of heavily pretreated HER2+ breast cancer patients.

” ‘I am thrilled to have been able to offer this therapy to a patient in her early 40s. She didn’t have any other great treatment options that we would have expected to have any meaningful impact, especially on her brain. Now she’s been on the study over a year. The mets in her body are gone and the brain lesion has shrunk down to a little nubbin. She’s living a normal life, fretting about the family business and how the kids are doing – normal stuff,’ says Virginia Borges, MD, MMSc, director of the Breast Cancer Research Program and Young Women’s Breast Cancer Translational Program at the University of Colorado Cancer Center and one of the study’s authors.

“Both sets of results being presented are from ongoing phase 1b clinical trials of ONT-380, one in combination with the drug TDM-1, and the other in combination with capecitabine and/or trastuzumab. Women on these studies include those whose disease had progressed after at least two previous rounds of therapy (sometimes including previous drugs used to target HER2).”

Blood Thinner Safe for Cancer Patients with Brain Metastases

“Cancer patients with brain metastases who develop blood clots may safely receive blood thinners without increased risk of dangerous bleeding, according to a study, published online today in Blood, the Journal of the American Society of Hematology

“Cancer increases a patient’s risk of developing blood clots. When a patient with cancer develops a clot, treatment with a blood thinning medication called an anticoagulant is often added to their treatment regimen in order to prevent the potentially fatal complication of blood clots traveling to the lungs. However, if cancer spreads to the brain, anticoagulant treatment may be withheld because it could cause dangerous bleeding in the patient’s head, which is already a risk for these patients. The task of preventing dangerous blood clots and avoiding life-threatening bleeding presents a particular challenge for specialists in patients with tumor metastases in the brain. Until recently, no data had confirmed whether blood thinners could be safely administered in these patients.

“In order to determine whether administering blood-thinning medication to patients with brain metastases and blood clots increases bleeding, researchers studied the medical records of 293 patients, 104 of whom had received a widely used blood thinner (enoxaparin). The remaining 189 patients did not receive blood-thinning treatment. Researchers matched the patients in each group by year of brain metastases diagnosis, tumor type, age, and gender.”

Roche: "Investigational Medicine Alectinib Shrank Tumours in Nearly Half of People with Specific Type of Lung Cancer"

“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced positive results from two pivotal studies (NP28673 and NP28761) that showed alectinib, its oral investigational anaplastic lymphoma kinase inhibitor (ALKi), shrank tumours (overall response rate; ORR: 50% and 47.8%, respectively) in people with advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC) whose disease had progressed following treatment with crizotinib. In addition, alectinib was shown to shrink tumours in people whose cancer had spread to the central nervous system (CNS) (CNS ORR: 57.1% and 68.8%, respectively). Additionally, people whose tumours shrank in response to alectinib continued to respond for a median of 11.2 and 7.5 months, respectively (duration of response; DOR). Alectinib demonstrated a safety profile consistent with that observed in previous studies. The most common adverse events (Grade 3 or higher occurring in at least 2% of people) were an increase in muscle enzymes (increased blood levels of creatine phosphokinase), increased liver enzymes and shortness of breath (dyspnea).1,2

“ ‘Cancer spreads to the brain in about half of people with ALK-positive lung cancer, and these studies suggest that alectinib can shrink tumours in people with this difficult-to-treat disease,’ said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. ‘We plan to submit these data to the FDA this year to support alectinib as a potential new option for people whose advanced ALK-positive lung cancer progressed on crizotinib.’ “

Brigatinib Achieves Brain Metastases Control for Over 80% of ALK-Positive NSCLC Patients

“Brigatinib (AP26113), an investigational ALK tyrosine kinase inhibitor, demonstrated significant intracranial antitumor activity in patients with ALK-positive non–small cell lung cancer (NSCLC) and brain metastases, according to findings presented at the European Lung Cancer Conference.1

“A post hoc analysis conducted by Ariad Pharmaceuticals, the company developing brigatinib, looked at 49 NSCLC patients identified as having baseline brain metastasis. The analysis determined that intracranial disease control was achieved with brigatinib in 87% of patients with measurable brain metastases and in 87% of patients with nonmeasurable brain metastases. Intracranial response was reported in 53% of patients with measurable brain metastases and in 30% of patients with nonmeasurable lesions.

“Following treatment, 45 patients achieved median intracranial progression–free survival (PFS) of 22.3 months. The median duration of intracranial response was 18.9 months.

“Adverse events were mild to moderate in severity and included nausea, diarrhea, and fatigue that were reported by 29 (59%), 28 (57%), and 24 (49%) patients, respectively.”