FDA Approves Brigatinib to Treat Frontline ALK-Positive NSCLC

The FDA has approved brigatinib (Alunbrig) for the first-line treatment of patients with ALK-positive metastatic non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.

“We’re extremely proud of the positive results Alunbrig has shown for newly diagnosed ALK-positive NSCLC patients, particularly those with brain metastases,” Teresa Bitetti, president, Global Oncology Business Unit, Takeda, said in a press release. “Through a robust clinical development program and ongoing investigations across the NSCLC treatment landscape, Takeda is committed to uncovering solutions for people living with devastating forms of lung cancer in need of new options. We believe this approval for ALUNBRIG is a substantial step in the right direction and represents significant progress for Takeda’s broader lung cancer portfolio.”

The approval is based on the international, open-label, comparative, multicenter, phase III ALTA-1L trial, designed to evaluate the efficacy and safety of brigatinib with crizotinib in 275 patients with stage IIIB/IV ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor, but may have received ≤1 prior regimen of chemotherapy in the advanced setting.

Patients were randomized 1:1 to receive either 180 mg of brigatinib once daily (n = 137), with a 7-day lead-in period at 90 mg, or 250 mg of crizotinib twice daily (n = 138). Crossover from the crizotinib arm to receive brigatinib was permitted at blinded independent review committee-assessed progression-free survival (PFS).

The primary endpoint was blinded independent review committee-assessed PFS, and secondary endpoints included objective response rate (ORR) per RECIST v1.1 criteria, intracranial ORR, intracranial PFS, overall survival (OS), safety, and tolerability.

Treatment with brigatinib demonstrated a 51% reduction in the risk of disease progression or death compared with crizotinib (Xalkori) in patients with advanced ALK-positive NSCLC who had not received a prior ALK inhibitor.

The 2-year investigator-assessed results showed that brigatinib led to a 76% (HR, 0.24; 95% CI, 0.12-0.45) reduction in the risk of disease progression or death in newly diagnosed patients who had brain metastases at time of enrollment.

As of data cutoff on June 28, 2019, results showed that by blinded independent review committee assessment, there was a 51% reduction in the risk of disease progression or death with brigatinib over crizotinib (HR, 0.49; 95% CI, 0.35-0.68; log-rank P <.0001).

Confirmed ORR was 74% with brigatinib and 62% for crizotinib; the median duration of response (DOR) was not reached (95% CI, 19.4–NE) and 13.8 months (95% CI, 9.3-8) with brigatinib and crizotinib, respectively. When assessed by blinded independent review committee, brigatinib reduced the risk of intracranial disease progression or death by 69% in patients with brain metastases at baseline (HR, 0.31; 95% CI, 0.17-0.56).

The median intracranial PFS was 24 months compared with 5.6 months for crizotinib; the median PFS was not reached with brigatinib and was 5.9 months with crizotinib, as assessed by investigators. Moreover, the confirmed intracranial ORR for patients with measurable brain metastases at baseline was 78% for patients treated with brigatinib and 26% for those who received crizotinib. The median intracranial DOR in confirmed responders with measurable brain metastases at baseline was not reached with brigatinib and 9.2 months with crizotinib, respectively.

“Results from the ALTA 1L trial add brigatinib to the very short list of first-line treatment options for ALK-positive lung cancer patients that have proven to be superior to crizotinib. Compared to crizotinib, brigatinib demonstrated superior efficacy, especially among those with brain metastases at baseline, and a low pill burden, at one pill a day, which is an important factor when we could be controlling disease for years,” Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research, University of Colorado Cancer Center, said in the release. “These data have established brigatinib’s potential in the first-line setting, and I’m confident the FDA approval will open a new window of possibilities for physicians and their patients.”