Diagnosis of adenocarcinoma of the lung, a major subtype of non-small lung cancer (NSCLC), nowadays triggers mandatory testing of tumor tissue for alterations in four genes: EGFR, ALK, ROS1, and more recently, BRAF. If present, these alterations predict sensitivity to specific targeted drugs approved by the U.S. Food and Drug Administration (FDA) that work better and often longer than standard chemotherapy, and are better tolerated.
However, there are many more targetable/actionable genomic alterations (also known as “drivers”) in NSCLC. This blog post will briefly discuss most of them, with the goal of promoting molecular testing for more than the four “usual suspects” mentioned above. Some patients with these alterations may benefit from FDA-approved drugs or from enrollment in clinical trials that are testing additional drugs and drug combinations. Continue reading…
“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from the global phase III ALUR study showing that Alecensa® significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by 85% compared to chemotherapy in patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC), who had progressed following treatment with platinum-based chemotherapy and crizotinib (hazard ratio [HR]=0.15, 95% CI: 0.08-0.29, p<0.001). Median PFS reported by the investigators, the primary endpoint of the study, was 9.6 months in patients who received Alecensa (95% CI: 6.9-12.2) compared with 1.4 months (95% CI: 1.3-1.6) in those who received chemotherapy. Median PFS assessed by an independent review committee (IRC), a secondary endpoint, was 7.1 months for patients who received Alecensa versus 1.6 months for patients who received chemotherapy (HR=0.32, 95% CI 0.17–0.59; p<0.001). The safety profile of Alecensa was consistent with that observed in previous studies and compared favourably to chemotherapy.”
“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.”
“Ceritinib appeared safe and effective in patients with ROS1–rearranged non–small cell lung cancer, according to a multicenter, open-label phase 2 study.
“ALK inhibitors — especially crizotinib (Xalkori, Pfizer) — effectively treat ROS1–positive cell lines and tumors. However, patients eventually develop resistance and experience a high incidence of brain recurrence.
” ‘Treatment options beyond crizotinib are needed, and clinical development of other ROS1 inhibitors should be accelerated to improve treatment outcome of patients with ROS1–positive NSCLC,’ Byoung Chul Cho, MD, PhD, assistant professor at Yonsei Cancer Center of Yonsei University College of Medicine, and colleagues wrote.”
“Findings from a phase III clinical trial point to a more effective initial treatment for patients with ALK-positive non-small cell lung cancer (NSCLC). Compared to the current standard of care crizotinib (Xalkori), the newer ALK inhibitor alectinib (Alecensa) halted cancer growth for a median of 15 months longer and caused fewer severe side effects.
“The study will be featured in a press briefing today and presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.”
“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.”
“Roche has presented late-stage data showing that its Alecensa was superior to Pfizer’s Xalkori on progression-free survival in patients with a specific type of lung cancer.
“The global, randomised Phase III ALEX study hit its primary endpoint in showing that Alecensa (alectinib) as a first-line treatment significantly reduced the risk of disease worsening or death (progression-free survival, PFS) versus Xalkori (crizotinib) in people with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).”
“Currently available as a second-line therapy for patients with ALK-positive non–small cell lung cancer (NSCLC), alectinib’s (Alecensa) frontline potential is being explored in the ongoing phase III ALEX study (NCT02075840), which could transform first-line treatment for these patients.
“This study is comparing alectinib with crizotinib (Xalkori)—a current first-line option—in the frontline setting for patients with ALK-positive NSCLC. The oncology community is anticipating reports on the data in the first half of 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.’ ”