“Adult patients with ALK-positive, locally advanced or metastatic non–small cell lung cancer (NSCLC) who had not received a prior ALK inhibitor experienced a more than 50% reduction in the risk of disease progression or death with treatment with brigatinib (Alunbrig), compared with the first-line standard of care, crizotinib.
“Brigatinib demonstrated superior progression-free survival (PFS) compared with crizotinib, corresponding to a 51% reduction in the risk of disease progression or death (HR, 0.49; 95% CI, 0.33-74; P = .0007), according to first interim analysis results presented at the 19th World Conference on Lung Cancer and simultaneously published in the New England Journal of Medicine.”
“Brigatinib conferred substantial intracranial responses and durable PFS among patients with brain metastases and ALK-positive, non-small cell lung cancer previously treated with crizotinib, according to ongoing study results.
” ‘Crizotinib [Xalkori; Pfizer, EMD Serono], the first licensed ALK inhibitor, is very active but has clear central nervous system liability from poor CNS penetration. All of the next-generation ALK inhibitor drugs have started to show CNS efficacy consistent with their superior activity in the brain compared with crizotinib,’ D. Ross Camidge, MD, PhD, director of thoracic oncology at University of Colorado, told HemOnc Today. ‘The whole clinical trials field has had to evolve around these events in terms of how we should capture and present CNS data. Brigatinib [Alunbrig; Takeda Oncology, Ariad] was one of the drugs that helped with this.’ ”
“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.”
“About 3-5 percent of lung cancers are caused by changes in the gene ALK. In 2011, the FDA granted accelerated approval for the drug crizotinib to target these ALK changes. However, two major problems have remained: Crizotinib does not pass into the brain and so is unable to target ALK-positive lung cancer in the central nervous system, and the genetic diversity of cancer allows the later growth of subpopulations that can resist the drug, leading to renewed growth. In response, researchers have been actively developing next-generation ALK-inhibitors.
“Results of a multi-center, 222-person phase 2 clinical trial of the next-generation ALK inhibitor, brigatinib at 180mg/day, used after failure of crizotinib showed a 54 percent response rate and 12.9 month progression-free survival. (Effects were lower at a lower dose.) Results are published in the Journal of Clinical Oncology.”
“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.”
“Ongoing clinical trials and a novel agent recently submitted to the FDA could expand the armamentarium for ALK-positive non–small cell lung cancer (NSCLC). Approved agents in the setting include the ALK inhibitors crizotinib (Xalkori), ceritinib (Zykadia), and alectinib (Alecensa).
“A new drug application (NDA) was submitted for brigatinib (AP26113) in August 2016 as a potential treatment for patients with ALK-positive disease. The NDA is partly based on encouraging results from the phase II ALTA study, which demonstrated a confirmed objective response rate of 54% for brigatinib at the 180 mg daily dose, including a 4% complete response rate.”
“A new drug application (NDA) has been submitted for brigatinib (AP26113) as a potential treatment for patients with advanced ALK-positive non–small cell lung cancer (NSCLC) following resistance or intolerance to crizotinib (Xalkori), according the developer of the ALK inhibitor, Ariad Pharmaceuticals.
“The application was based on findings from the phase II ALTA study, which was presented at the 2016 ASCO Annual Meeting, along with results from an earlier phase I/II trial. In ALTA, the confirmed objective response rate (ORR) for brigatinib at 180 mg daily was 54%, which included a complete response rate of 4%. In those with measurable, active brain metastases treated with the 180 mg dose (n = 18), the intracranial ORR was 67%. Median progression-free survival (PFS) was 12.9 months.”
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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…