Lorlatinib Shows Promise Against Brain Metastases in ALK+ Lung Cancer

Excerpt:

“Lorlatinib exhibits durable responses in pretreated patients with ALK-positive non–small-cell lung cancer (NSCLC) and promising intracranial activity and tumor responses in those patients who have brain metastases, regardless of prior therapy, according to findings from a phase I/II clinical study (abstract 9006) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.

” ‘Lorlatinib demonstrated clinically meaningful and durable responses in ALK-positive patients receiving one or more prior ALK TKI [tyrosine kinase inhibitor], many of whom were heavily pretreated,’ said coauthor Sai-Hong Ignatius Ou, MD, of the University of California Irvine Chao Family Comprehensive Cancer Center in Orange, California.”

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Nivolumab/Ipilimumab Highly Active in Patients With Melanoma Brain Metastases

Excerpt:

“Nivolumab plus ipilimumab demonstrated an intracranial response (ICR) rate of 42% in asymptomatic patients with melanoma brain metastases who had not received prior local therapy to the brain.

“In the phase II Anti-PD1 Brain Collaboration (ABC) trial, the 6-month intracranial PFS rate was 46% with the anti–PD-1/CTLA-4 combination.

” ‘The combination of nivolumab and ipilimumab has high activity in melanoma brain metastases and may be considered for upfront therapy in such patients,’ said lead author Georgina V. Long, BSc, PhD, MBBS, clinical researcher at the Melanoma Institute Australia and Westmead Hospital in Sydney.”

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Two Combination Therapies Shrink Melanoma Brain Metastases in More Than Half of Patients

Excerpt:

“High response rates to a pair of combination therapies point to potentially new options for a group of metastatic melanoma patients who have been largely left out of recent treatment progress – those whose disease has spread to the brain.

“A combination regimen of two immunotherapies and another of two targeted therapies each significantly shrank metastatic in at least 50 percent of patients in separate multi-center clinical trials presented today at the 2017 ASCO Annual Meeting by principal investigators from The University of Texas MD Anderson Cancer Center.”

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Study Suggests Best Order of Treatment for Brain Metastases in EGFR Lung Cancer

Excerpt:

“About 10 percent of lung cancers in the United States and as many as 40 percent in Asia are driven by mutations in the EGFR gene. EGFR targeted treatment advances over the previous decade now result in multiple options for controlling the disease in the body, but due to the reduced ability of many of these drugs to penetrate into the brain, treating of disease in the brain remains challenging. When brain metastases are seen at diagnosis before a patient has tried EGFR-targeted drugs, it has been an open question whether doctors should try drugs alone just in case they work in the brain or move directly to whole-brain radiotherapy or stereotactic radiosurgery (a tightly focused form of radiation) first, followed by targeted medicines. A study published in the Journal of Clinical Oncology looks back at 351 patients with EGFR mutant lung cancer and brain metastases treated at six institutions to offer compelling preliminary evidence as to the best sequence of these techniques: Radiation followed by targeted medicines resulted in the longest overall survival.”

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Brain Mets Can Acquire HER2-Positivity in HER2-Negative Breast Cancer Patients

Excerpt:

“Brain metastases from primary breast cancer tumors often acquire clinically actionable genetic alterations, according to a small study. About one fifth of ERBB2/HER2-negative cases switched to HER2-positivity in the brain metastases.

” ‘Limited therapeutic options exist for patients with brain metastases,’ wrote study authors led by Nolan Priedigkeit, BS, of the University of Pittsburgh. ‘ERBB2/HER2-positive brain metastases have demonstrated encouraging responses to ERBB2/HER2-targeted therapies in recent clinical trials.’ ERBB2/HER2-negative brain metastases, however, have shown no such response.”

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A Breast Cancer Drug That Gets In The Brain? Cascadian Sees A Way Forward

Excerpt:

“Breast cancer patients sometimes end up dying when their tumors spread all the way to the brain. Some very good drugs already exist for patients with breast cancer, especially ones with tumors that overexpress the HER2 marker, but that success has raised a new question: Can drugmakers take another step, and fight those deadly brain metastases that get people in the end?

“Seattle-based Cascadian Therapeutics is testing that idea this week with researchers gathered at the San Antonio Breast Cancer Symposium. Cascadian is reporting today that patients who got conventional capecitabine and trastuzumab, plus an experimental small-molecule drug, tucatinib (aka ONT-380), lived a median of 7.8 months without their tumors getting worse. About 61% of patients on that triple-drug combo saw tumors shrink. It’s an impressive result, given that these patients were especially ill when they enrolled in the study, having already received a median of three prior rounds of HER2-targeted therapy. The data are also holding up over time: a snapshot of the data from June showed patients living a median of 6.3 months without their tumors spreading.”

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Icotinib Improves Intracranial PFS in EGFR-Mutant NSCLC and Brain Mets

Excerpt:

“Treatment with icotinib more than doubled intracranial progression-free survival (iPFS) compared with whole brain irradiation (WBI) combined with standard chemotherapy, according to phase III trial results presented at the 17th World Lung Cancer Conference, the Annual Meeting of the International Association for the Study of Lung Cancer (IASLC), in Vienna.

“Icotinib significantly improved median iPFS, the trial’s primary endpoint, to 10.0 months compared with 4.8 months in patients treated with WBI and chemotherapy, HR = 0.56; 95% CI, 0.36-0.90 (P = .014). Secondary endpoints of the trial, including progression-free survival (PFS) and the objective response rate (ORR), were also significantly improved with icotinib over WBI/chemotherapy. Median PFS was 6.8 versus 3.4 months, respectively (HR, 0.44; 95% CI, 0.31-0.63 [P < .001]).”

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Angiochem’s ANG1005 Shows Clinical Benefits and Prolonged Survival for Breast Cancer Patients With Brain Metastases

Excerpt:

“Angiochem, a biotechnology company developing peptide-drug conjugates uniquely capable of crossing the blood-brain barrier, recently presented data from its Phase II trial for its lead compound, ANG1005, at two highly regarded international cancer conferences: The European Society for Medical Oncology (ESMO) 2016 Congress and the European Association of Neuro-Oncology (EANO) 2016 Meeting.

“On Friday Oct 7th, 2016 at the ESMO Congress, Copenhagen, Denmark, Shou-Ching Tang, MD, PhD Leader, Breast Cancer Multidisciplinary Program, Augusta University, Augusta, GA, USA presented a podium presentation titled: ANG1005, a novel peptide-paclitaxel conjugate crosses the BBB and shows activity in patients with recurrent CNS metastasis from breast cancer, results from a phase II clinical study.”

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Immune and Targeted Therapies Combined with Radiation Therapy Improves Outcomes for Melanoma Brain Metastases Patients, Say Moffitt Researchers

Excerpt:

“Brain metastases are one of the most common complications of advanced melanoma, requiring multidisciplinary management. Patients who are diagnosed with these metastases have an expected median survival of only 4 to 5 months. Moffitt Cancer Center researchers hope to improve these survival rates following a new study in Annals of Oncology that shows novel immune and targeted therapies with radiation therapy improves the outcomes of patients with melanoma brain metastases over conventional chemotherapy.”

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