Julia Rotow, MD, medical oncologist, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, discusses remaining questions with brigatinib (Alunbrig) in 

-positive non&shy;—small cell lung cancer (NSCLC).

Recently, updated data from the phase III ALTA-1L trial demonstrated an improvement in median progression-free survival with first-line brigatinib versus crizotinib (Xalkori) in patients with ALK inhibitor—naïve, advanced 

Though brigatinib is not approved for frontline therapy in this space, Rotow believes the field will want to define the utility of brigatinib versus alectinib (Alecensa) in the frontline setting. The toxicities that are associated with the agents will likely be a determining factor in treatment selection. 

Additionally, more research regarding the development of targeted therapies for patients who develop 

-independent resistance is needed, concludes Rotow.

Videos

Julia Rotow, MD, discusses remaining questions with brigatinib in ALK-positive non&shy;–small cell lung cancer.

Dr. Rotow on Remaining Questions With Brigatinib in ALK+ NSCLC

Julia Rotow, MD, medical oncologist, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, discusses the implications of next-generation ALK inhibitors in non—small cell lung cancer (NSCLC).

An increasing number of next-generation ALK inhibitors is emerging for the treatment of patients with 

As such, upfront molecular testing with next-generation sequencing is critical to identify patients with an 

Additionally, patients with central nervous system (CNS) disease should be considered for treatment with next-generation agents such as alectinib (Alecensa) or brigatinib (Alunbrig) as they have demonstrated marked CNS activity, explains Rotow.

Starting a patient on systemic therapy may initially spare them the toxicities associated with radiation, while allowing them to achieve good disease control, concludes Rotow.

Julia Rotow, MD, discusses the implications of next-generation ALK inhibitors in non–small cell lung cancer.

Dr. Rotow on the Implications of Next-Generation ALK Inhibitors in NSCLC

Julia Rotow, MD, medical oncologist, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, discusses the utility of brigatinib (Alunbrig) versus crizotinib (Xalkori) for the first-line treatment of patients with 

-positive non—small cell lung cancer (NSCLC).

The phase III ALTA-1L trial randomized 275 ALK inhibitor—naïve patients with 

-positive disease to brigatinib or crizotinib (Xalkori), says Rotow. The trial design was similar to that of the phase III ALEX trial, which randomized patients to alectinib (Alecensa) or crizotinib in the same setting.

Initial results from ALTA-1L demonstrated improved progression-free survival (PFS) with brigatinib compared with crizotinib. Recently, updated findings from the trial showed continued PFS benefit at 2 years, as well as an improved objective response rate with brigatinib versus crizotinib.

In April 2017, the FDA granted an accelerated approval to brigatinib for the treatment of patients with 

-positive NSCLC who progressed on or are intolerant of crizotinib. (Xalkori).

Regulatory approval of first-line brigatinib may be contingent on long-term follow-up and overall survival data; however, the results that have been reported to date suggest brigatinib will be added to the armamentarium as another option for 

Julia Rotow, MD, discusses the utility of brigatinib versus crizotinib for the first-line treatment of patients with ALK-positive non

Dr. Rotow on First-Line Brigatinib Versus Crizotinib in ALK+ NSCLC

Julia Rotow, MD, medical oncologist, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, discusses updated data from the phase III ALEX trial in ALK-positive non—small cell lung cancer (NSCLC).

The ALEX trial randomized patients with newly diagnosed ALK-positive NSCLC to receive alectinib (Alecensa) or crizotinib (Xalkori).

Initial results showed an improvement in progression-free survival (PFS) and central nervous system (CNS) activity with alectinib versus crizotinib, says Rotow.

According to 42-month follow-up data which were published in the 

 in May 2019, the median PFS was 34.1 months with alectinib versus 10.2 months with crizotinib. Additionally, alectinib showed superiority over crizotinib in patients regardless of baseline CNS metastases. Overall survival (OS) data are immature, but a trend toward survival benefit was reported with alectinib compared with crizotinib, says Rotow.

At the 2019 ESMO Congress, mature PFS data, as well as updated OS and safety data were presented.

Julia Rotow, MD, discusses updated data from the phase III ALEX trial in ALK-positive non–small cell lung cancer.

Dr. Rotow on Updated ALEX Trial Results in ALK+ NSCLC

Julia Rotow, MD, medical oncologist, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, discusses the safety profile of brigatinib (Alunbrig) in 

In 2017, the FDA announced accelerated approval of brigatinib for patients with metastatic 

-positive NSCLC who are resistant to prior crizotinib.

Brigatinib has shown similar toxicity to available ALK TKIs, including gastrointestinal adverse events, explains Rotow. Other toxicities such as elevated blood pressure, creatine phosphokinase, and lipase appear to be more specific to brigatinib, she continues.

Importantly, a pulmonary toxicity syndrome may develop in some patients treated with brigatinib within the first week or so of therapy. This syndrome can present with shortness of breath or infiltrates on lung imaging, Rotow says.

A dose-escalation regimen with brigatinib may mitigate this toxicity, concludes Rotow. Patients should have a 1-week 90 mg lead-dose of the drug, with an increased 180 mg dose given if initial therapy is well tolerated.

Julia Rotow, MD, discusses the safety profile of brigatinib in ALK-positive non–small cell lung cancer.

Julia Rotow, MD

Articles

Dr. Rotow on Remaining Questions With Brigatinib in ALK+ NSCLC

Dr. Rotow on the Implications of Next-Generation ALK Inhibitors in NSCLC

Dr. Rotow on First-Line Brigatinib Versus Crizotinib in ALK+ NSCLC

Dr. Rotow on Updated ALEX Trial Results in ALK+ NSCLC

Dr. Rotow on Brigatinib Safety Profile in ALK+ NSCLC