“Doubling the dose of the ALK inhibitor brigatinib (Alunbrig) improved outcomes in patients with crizotinib (Xalkori)-refractory non-small cell lung cancer (NSCLC), a dose-comparison study showed.
“Patients who started treatment at 90 mg/day and titrated to 180 mg/day had improved response rate (54% versus 45%) and progression-free survival (PFS) as compared with those who received 90 mg throughout the treatment period. Response in brain metastases improved by 50% with the higher dose.”
“On Friday evening, Takeda Pharmaceuticals announced the FDA has approved Alunbrig (brigatinib) to treat patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.
“Brigatinib is a kinase inhibitor that can be taken orally. The recommended dose is 90 mg orally once daily for the first 7 days. If 90 mg is tolerated during the first 7 days, patient should increase the dose to 180 mg orally once daily. The pill can be taken with or without food.”
“The FDA has has granted a priority review to a new drug application (NDA) for brigatinib for patients with metastatic ALK-positive non–small cell lung cancer (NSCLC) who are resistant to prior crizotinib (Xalkori), according to a statement from the drug’s developer, Ariad Pharmaceuticals.
“The NDA, which follows a breakthrough therapy designation that was received in October 2014, is based on findings from the phase II ALTA trial. In results from the trial presented at the 2016 ASCO Annual Meeting, the confirmed objective response rate (ORR) for brigatinib at 180 mg daily was 54% and the median progression-free survival (PFS) was 12.9 months. Under the Prescription Drug User Fee Act, the FDA is scheduled to make a final decision on the NDA by April 29, 2017.”
“Ceritinib provides longer progression-free survival than chemotherapy in crizotinib-pre-treated patients with non-small-cell lung cancer harbouring an ALK rearrangement, according to results of the phase III ASCEND-5 study presented at the ESMO 2016 Congress in Copenhagen.
” ‘Patients with non-small cell lung cancer (NSCLC) should receive front line therapy with the anaplastic lymphoma kinase (ALK) inhibitor crizotinib,’ said lead author Professor Giorgio Scagliotti, head of the Department of Oncology, University of Turin, Italy. ‘Most patients develop resistance to crizotinib and currently second line treatment is represented by chemotherapy alone.’ ”
This year, the Annual Meeting of the American Society of Clinical Oncology (ASCO) did not produce any truly groundbreaking revelations about new treatments for lung cancer. However, researchers did report quite a few positive findings, and some disappointing ones. I have summarized some of the more prominent presentations below. Continue reading…
“The investigational tyrosine kinase inhibitor (TKI) brigatinib offered good response rates in a pivotal phase II trial of patients with ALK-positive non–small-cell lung cancer (NSCLC) whose disease progressed on crizotinib. The results were presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 9007).
“ ‘Most ALK-positive NSCLC patients treated with crizotinib eventually progress, often due to acquired ALK resistance mutations and/or poor CNS drug penetration,’ said Dong-Wan Kim, MD, PhD, of Seoul National University Hospital in South Korea, who presented the study.
“Brigatinib, a next-generation ALK TKI designed to have broad activity against resistant ALK mutants, showed promising clinical activity in a phase I/II study of crizotinib-treated ALK-positive NSCLC patients. The new open-label phase II ALTA study included 222 patients with locally advanced or metastatic NSCLC who had progressive disease on crizotinib. Patients were randomized to two brigatinib treatment regimens: group A (112 patients) received oral brigatinib 90 mg once per day, and group B (110 patients) received the same dose for 7 days followed by 180 mg once per day.”
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“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).”
“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]).”
“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.”