Alectinib Highly Active in Advanced ALK-Positive NSCLC

“Alectinib showed promising activity in patients with advanced, crizotinib-refractory, ALK-positive non–small cell lung cancer, according to results of a global phase 2 study.

“The regimen also appeared well tolerated.

“In December, the FDA granted accelerated approval to alectinib (Alecensa, Genentech) — an oral, small molecule, ATP-competitive tyrosine kinase inhibitor of ALK — for treatment of patients with metastatic ALK-positive NSCLC who progressed on or are intolerant to crizotinib (Xalkori, Pfizer).”


Personalizing Cancer Therapies May Combat Resistance to Targeted Therapy Drugs

“The use of drugs that target genetic mutations driving the growth of tumors has revolutionized treatment for several serious forms of cancer, but in almost every case, tumors become resistant to the drugs’ therapeutic effects and resume growth, often through the emergence of new mutations, which has spurred the development of more powerful drugs that can overcome resistance mutations. In the Dec. 24 issue of New England Journal of Medicine, Massachusetts General Hospital (MGH) physicians report their study examining the evolution of drug resistance in a lung cancer patient treated with multiple different targeted therapies. When resistance developed to the third targeted therapy, the new mutation actually restored the cancer’s response to the very first targeted therapy drug used to treat the patient.”


FDA Grants Genentech’s Alecensa® (Alectinib) Accelerated Approval for People with a Specific Type of Lung Cancer

“Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) granted accelerated approval to Alecensa® (alectinib) for the treatment of people with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. In the pivotal studies, Alecensa shrank tumors in up to 44 percent of people with ALK-positive NSCLC who progressed on crizotinib (objective response rate [ORR] of 38 percent [95 percent CI 28-49] and 44 percent [95 percent CI 36-53]). In a subset of people with tumors that spread to the brain or other parts of the central nervous system (CNS), Alecensa shrank CNS tumors in about 60 percent of people (CNS ORR of 61 percent [95 percent CI 46-74]).”


FDA Grants Priority Review to Xalkori for New Indication in NSCLC

“The FDA granted priority review to a supplemental new drug application for crizotinib.

“Crizotinib (Xalkori, Pfizer) — a kinase inhibitor — already is approved for treatment of patients with metastatic ALK-positive non–small cell lung cancer.

“The supplemental application requests that the approval be expanded to allow crizotinib to be used for treatment of patients with metastatic ROS1-positive NSCLC. The FDA granted breakthrough therapy designation to crizotinib for this indication in April.

“ROS1 rearrangement occurs in an estimated 1% of NSCLC cases, according to a Pfizer-issued press release.”


Crizotinib Granted FDA Priority Review for ROS1 mNSCLC

“The FDA has granted a priority review for a supplemental new drug application (sNDA) for crizotinib (Xalkori). The application is for an indication in patients with metastatic non–small cell lung cancer (NSCLC), whose tumors are ROS1-positive, according to a press release posted by Pfizer Inc.

” ‘ROS1 is another gene rearrangement. It is like ALK in that it is structurally related, but rarer. ROS1 occurs in about 1% of [NSCLC] patients, but [it has] also been seen in other types of rare cancers,’ said D. Ross Camidge, MD, PhD, director, Thoracic Oncology Clinical Program, University of Colorado Cancer Center, in an interview with Targeted Oncology. He added that crizotinib, originally an ALK inhibitor, may be even more effective as a ROS1 inhibitor. ‘It’s great for that small population of patients.’ “


Alectinib Shows Response in Crizotinib-Refractory NSCLC

“The ALK inhibitor alectinib was highly active and well-tolerated in patients with ALK-rearranged, crizotinib-refractory, advanced non–small-cell lung cancer (NSCLC), according to results of a phase II trial.

“In this trial, 138 patients with crizotinib-refractory ALK-positive NSCLC were treated with alectinib; 122 of these patients were evaluable for response, and 61% had central nervous system (CNS) metastases at baseline. The results were published in the Journal of Clinical Oncology.

“ ‘Almost all patients invariably experience progression on crizotinib, and approximately 40% of the patients with ALK-rearranged NSCLC develop CNS metastases as an initial site of progression,’ wrote study authors led by Sai-Hong Ignatius Ou, MD, PhD, of the Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine in Orange, California. Alectinib is approximately five times as potent an ALK inhibitor as crizotinib, and can inhibit most of the acquired ALK resistance mutations to crizotinib.”


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).”


Pfizer Reports Positive Topline Results from Phase 3 Trial Comparing XALKORI® (crizotinib) to Chemotherapy in Previously Untreated East Asian Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

“Pfizer Inc. announced today that PROFILE 1029, a Phase 3 study of anaplastic lymphoma kinase (ALK) inhibitor XALKORI® (crizotinib), met its primary objective of significantly prolonging progression-free survival (PFS) in previously untreated East Asian patients with ALK-positive advanced non-small cell lung cancer (NSCLC) when compared to a standard chemotherapy doublet. In this study, XALKORI was used as the first systemic therapy for patients with advanced ALK-positive NSCLC, and patients could have received therapy and/or surgery for early stage disease before they were diagnosed with metastatic disease.

“The adverse events observed with XALKORI in the study were generally consistent with findings from previous trials. No unexpected adverse events were observed. Efficacy and safety data from PROFILE 1029 will be submitted for presentation at a future medical meeting.”


Super Patient: Janet Freeman-Daily Joins a Clinical Trial—and Beats the Odds on Lung Cancer


In March 2011, Janet Freeman-Daily was about to take a long family trip to China. She’d been coughing for a while, so she asked her doctor for an antibiotic as a precaution before leaving. Even so, she came back in May with a respiratory infection that wouldn’t go away.

Her doctor ordered an X-ray and then a CT scan. “Before I got home, they called and said they’d like to do a bronchoscopy,” Janet says. The scan revealed a 7-cm mass in her left lung, and biopsies showed it was non-small cell lung cancer (NSCLC) and that it had spread to several lymph nodes. Continue reading…