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.’ ”


Improved Survival for Patients with Brain Mets Who Are 50 and Younger and Receive SRS Alone

“Cancer patients with limited brain metastases (one to four tumors) who are 50 years old and younger should receive stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT), according to a study available online, open-access, and published in the March 15, 2015 issue of the International Journal of Radiation Oncology * Biology * Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO). For patients 50 years old and younger who received SRS alone, survival was improved by 13 percentage points when compared to those patients 50 years old and younger who received both SRS and WBRT.

“This study, ‘Phase 3 Trials of Stereotactic Radiation Surgery With or Without Whole-Brain Radiation Therapy For 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis,’ analyzed patient data from the three largest randomized clinical trials (RCT) of SRS and WBRT conducted to-date: the Asian trial (JROSG99-1) by Aoyama et al.[1], published in 2006; the North American trial (MDACC NCT00548756) by Chang et al.[2], published in 2009; and the European trial (EORTC 22952-26001) by Kocher et al.[3], published in 2011. A total of 364 patients from the three RCTs were evaluated for this meta-analysis. Of those 364 patients, 51 percent (186) were treated with SRS alone, and 49 percent (178) received both SRS and WBRT. Nineteen percent of patients (68) were 50 years old and younger, and 61 percent (19) of these patients had a single brain metastasis. Twenty percent of all patients (72) had local brain failure, which is the occurrence of progression of previously treated brain metastases; and 43 percent (156) experienced distant brain failure, which is the occurrence of new brain metastases in areas of the brain outside the primary tumor site(s).

“The impact of age on treatment effectiveness revealed SRS alone yielded improved overall survival (OS) in patients 50 years old and younger. Patients 50 years old and younger who received SRS alone had a median survival of 13.6 months after treatment, a 65 percent improvement, as opposed to 8.2 months for patients 50 years old and younger who were treated with SRS plus WBRT. Patients >50 years old had a median survival of 10.1 months when treated with SRS alone, and 8.6 months for those who received SRS plus WBRT.”


Crizotinib Shows Promise against Brain Metastases in Patients with NSCLC

The gist: A drug called crizotinib (Xalkori) has shown promise for some people with non-small cell lung cancer (NSCLC) that has metastasized to the brain. Xalkori is already used to treat NSCLC in patients whose tumors have a genetic abnormality known as “ALK rearrangement.” A recent study focused specifically on people whose NSCLC had spread to the brain. The researchers found that Xalkori may help patients whose brain metastases have not yet caused any symptoms.


Puma Shrugs off an 'Expected' Phase II Failure for Its Breast Cancer Drug

The gist: A new breast cancer drug called neratinib works just as well as Herceptin for some HER2-positive patients. It may also reduce the chances of metastases in the central nervous system; for example, in the brain. Researchers recently tested neratinib in volunteer patients in a clinical trial. They compared it to the drug Herceptin, which is already used by many breast cancer patients. In the trial, neratinib was tested in combination with the chemotherapy drug paclitaxel in people with HER2-positive breast cancer. People who took the neratinib combination had similar survival rates as people who took Herceptin. They had a 52.6% reduction in central nervous system metastases.

“Puma Biotechnology’s ($PBYI) closely watched neratinib failed to beat out the blockbuster Herceptin in a mid-stage breast cancer trial, a miss the company said was no surprise as it touted success on a secondary goal.

“The company recruited 479 patients with HER2- positive breast cancer, testing whether a combination of neratinib and paclitaxel could better prolong progression-free survival (PFS) than a cocktail of Roche’s ($RHHBY) Herceptin and paclitaxel. In the end, median PFS for Puma’s drug came in at 16.6 months, while Herceptin clocked 16.7. And neratinib fared no better on its secondary endpoint, charting a 74.8% overall response rate compared to Herceptin’s 75.1%.

“But Puma is ‘very pleased with the results,’ CEO Alan Auerbach said in a statement, pointing to the secondary endpoint in which neratinib succeeded. The drug contributed to a 52.6% reduction in the incidence of central nervous system metastases–for instance cancer spreading to the brain–compared to the Herceptin arm, a statistically significant result that Puma believes could help differentiate neratinib on the market for breast cancer therapies.

” ‘As expected, there was no statistically significant difference in progression-free survival and objective response rate for the paclitaxel plus neratinib arm compared to the paclitaxel plus trastuzumab arm,’ Auerbach said. ‘However … while the development of other HER2-targeted drugs has produced a clinically meaningful benefit to patients with HER2 positive breast cancer, these drugs have had little impact on CNS metastases. As a result, we believe that there remains an unmet clinical need for reducing the incidence of CNS metastases, and the results of the NEfERTT study demonstrate that we may be able to provide this type of improvement with neratinib. ‘ “