Crizotinib Tops Chemo for ALK-Positive NSCLC With Brain Metastases

Excerpt:

“First-line crizotinib therapy offered better intracranial disease control rate (IC-DCR) than chemotherapy in patients with ALK-positive non–small-cell lung cancer (NSCLC) and stable treated brain metastases, according to results of a phase III study.

“Earlier results from the ongoing PROFILE 1014 trial showed that crizotinib offers better progression-free survival (PFS) and response rates compared with pemetrexed-platinum chemotherapy. ‘Although the development of targeted therapies has improved outcomes for selected patient populations with oncogenic driver mutations, brain metastases are frequent and result in significant morbidity and mortality in patients with lung cancer,’ wrote study authors led by Benjamin J. Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre in East Melbourne, Australia.”

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Zykadia Shows High Response Rate Against ALK-Rearranged NSCLC in Clinical Trial

Excerpt:

“Updated results of the phase I ASCEND-1 trial, reported by Kim et al in The Lancet Oncology, indicate that the ALK inhibitor ceritinib (Zykadia) produced high response rates in advanced ALK-rearranged non–small cell lung cancer (NSCLC), including intracranial disease, in both patients with and without prior ALK inhibitor treatment.

“In the open-label trial, 246 patients enrolled from 20 sites in 11 countries in Europe, North America, and Asia-Pacific between January 2011 and July 2013 received oral ceritinib at 750 mg/d. Patients had ALK-rearranged locally advanced or metastatic disease that had progressed despite standard therapy or for which there was no effective standard therapy. A total of 83 patients had received no prior ALK inhibitor treatment, and 163 had received crizotinib (Xalkori), with 5 also receiving alectinib (Alecensa) after crizotinib. In these two groups, 53% and 54% of patients were female, 58% and 66% were white, and 42% and 29% were Asian.”

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NMS-E973, a Novel Synthetic Inhibitor of Hsp90 with Activity in Models of Drug Resistance to Targeted Agents, Including Intracranial Metastases

“Recent developments of second generation Hsp90 inhibitors suggested a potential for development of this class of molecules also in tumors that have become resistant to molecular targeted agents. Disease progression is often due to brain metastases, sometimes related to insufficient drug concentrations within the brain. Our objective was to identify and characterize a novel inhibitor of Hsp90 able to cross the blood-brain barrier (BBB)…”


Advances in Therapy for Melanoma Brain Metastases

Melanoma cells frequently metastasize to the brain, and approximately 50% of patients with metastatic melanoma develop intracranial disease. Historically, central nervous system dissemination has portended a very poor prognosis. Recent advances in systemic therapies for melanoma, supported by improved local therapy control of brain lesions, have resulted in better median survival for these patients. We review current local and systemic approaches for patients with melanoma brain metastases.”