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…


Mutation Status Guides Advanced NSCLC Therapy

“The presence or absence of mutations in advanced non-small cell lung cancer (NSCLC) should guide selection of first-line systemic therapy, according to an updated clinical guideline from the American Society of Clinical Oncology.

“Patients with squamous-cell tumors that have no gene alterations should begin treatment with combination platinum-based cytotoxic chemotherapy, so long as they have good performance status (0 or 1). Optionally, bevacizumab (Avastin) may be added when the platinum agent is carboplatin. For patients with performance status 2, either chemotherapy or palliative care alone is an acceptable option.

“In the presence of sensitizing EGFR mutations, appropriate first-line therapy is afatinib (Gilotrif), erlotinib (Tarceva), or gefitinib (Iressa). Treatment should begin with crizotinib (Xalkori) when patients have tumors with ALK or ROS1 rearrangements, as published online in the Journal of Clinical Oncology.”


Alectinib Promising in ALK-Positive Advanced NSCLC

“The ALK and RET inhibitor alectinib yielded good response rates and was very well tolerated in a phase II trial of patients with advanced, ALK-positive non–small-cell lung cancer (NSCLC; abstract 8008). Results were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2, in Chicago.

“Crizotinib is currently the standard-of-care for advanced, treatment-naive ALK-positive NSCLC. ‘However, the median progression-free survival (PFS) for these patients on crizotinib is under 12 months,’ said Sai-Hong Ignatius Ou, MD, PhD, of the UC Irvine Medical Center in California. ‘This is in part due to development of ALK mutations that are resistant to crizotinib.’

“Alectinib is a next-generation inhibitor that is highly selective for ALK and RET; as an ALK inhibitor, Ou said, it is approximately five times as potent as crizotinib. It can inhibit the majority of clinically relevant acquired ALK mutations.”


Promising Trial of Brigatinib Shows All Next-Gen ALK Inhibitors May Not Be Created Equal

“Phase I/II clinical trial results reported at the American Society for Clinical Oncology (ASCO) Annual Meeting 2015 show promising results for investigational drug brigatinib against ALK+ non-small cell lung cancer (NSCLC), with 58 of 78 ALK+ patients responding to treatment, including 50 of 70 patients who had progressed after previous treatment with crizotinib, the first licensed ALK inhibitor. Progression-free survival (PFS) in patients previously treated with crizotinib was 13.4 months.

” ‘Although still only in an early phase trial, brigatinib is showing an objective response rate in approximately 70 percent of ALK-positive post-crizotinib and it’s showing about a year of progression-free survival. These results are among the best in the field, offering a lot of hope to people with ALK-positive ,’ says D. Ross Camidge, MD, PhD, director of thoracic oncology at the University of Colorado Cancer Center and the trial’s principal investigator.”