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.”


NKTR-102 Improves Survival in Women with Brain and Liver Metastases from Breast Cancer

“Nektar Therapeutics (NASDAQ: NKTR) announced topline results from its Phase 3 BEACON study evaluating single-agent NKTR-102 in patients with advanced breast cancer. BEACON compared NKTR-102 to an active control arm comprised of a single chemotherapy agent of physician’s choice (TPC) in patients who were heavily pre-treated with a median of three prior therapies for metastatic disease. In a topline analysis of 852 patients from the trial, NKTR-102 provided a 2.1 month improvement in median overall survival (OS) over TPC (12.4 months for patients receiving NKTR-102 compared to 10.3 months for patients receiving TPC). Based on a stratified log-rank analysis, the primary endpoint measuring the Hazard Ratio (HR) for survival in the NKTR-102 group compared to the active control arm was 0.87 with a p-value of 0.08, which did not achieve statistical significance.

“In a pre-specified subgroup of patients with a history of brain metastases, NKTR-102 showed an improvement of 5.2 months in median OS (10.0 months compared to 4.8 months, n=67, HR 0.51, p-value <0.01). The proportion of patients with brain metastases with 12-month survival was 44.4% in the NKTR-102 arm as compared to 19.4% in the control arm.”


Localized Radiation for Brain Mets Has Similar Recurrence Rate at Tumor Site as Whole-Brain Radiation, but More New Mets over Time

“In patients who had undergone surgery for brain metastases, the rate of recurrence at the resected site was similar between patients who received adjuvant whole-brain radiotherapy vs those who underwent adjuvant localized radiotherapy, according to a retrospective study by Hsieh et al in the journal Neurosurgery. However, localized radiotherapy was associated with a higher incidence of distant metastases.

“Surgery followed by adjuvant whole-brain radiotherapy is a well-established treatment for brain metastases, particularly in patients who have a limited number of brain metastases. Yet discussions continue as to whether these patients require whole-brain radiotherapy or can be treated with localized radiotherapy. Localized radiotherapy is associated with fewer side effects compared with whole-brain radiotherapy, but some studies have documented an association with an increased risk for development of new intracranial metastases.

“Thus, the investigators  conducted a study to examine the rate of brain metastases recurrence between patients treated with whole-brain radiotherapy vs localized radiotherapy. They also analyzed overall survival and the risk of development of leptomeningeal disease…

“The investigators stated, ‘Our results support the conclusion that adjuvant treatment with localized radiotherapy instead of whole-brain radiotherapy as adjuvant provides equivalent control at the resection cavity and radiosurgically treated lesions, with no detectable difference in overall survival.’ ”