Takeda announces positive new ALK+ lung cancer data as list of crizotinib successors widens
Takeda unveiled new Phase III frontline data for their ALK inhibitor at European Society for Medical Oncology Asia Congress, showing it could deter the spread of lung cancer for two years or more. But the trial compared the drug, Alunbrig (brigatinib), against an early inhibitor that is no longer best-in-class and the Japanese pharma will likely face significant competition if regulators grant an expanded label.
“It’s part of the next generation of ALK inhibitors,” Sanjay Popat, a thoracic oncologist at Royal Marsden Hospital and an investigator on the trial, Alta-1L, told Endpoints News. “The updated data really confirms that brigatinib is way superior to crizotinib.”
The trial compared brigatinib against crizotinib in 275 advanced non-small-cell-lung-cancer patients who tested positive for the ALK gene, and it produced results that don’t take a biostatistician to understand.
The review committee found patients on brigatinib went a median 24 months without the cancer spreading, hitting the primary endpoint. For crizotinib patients? 11 months. (Takeda investigators found a slightly higher PFS for brigatinib and a slightly lower PFS for crizotinib).
In patients whose cancer had spread to the brain — a notoriously-difficult place to deliver compounds, including crizotinib — before the start of the trial, the drug improved progression-free survival by 76% against the control arm, as assessed by investigators.
“It’s designed to cross the blood-brain barrier,” Popat said of the drug. Patients with brain metastases represented about 30% of each arm.
The problem for Takeda is that the ALK-landscape has changed considerably since the Phase III trial began and since they acquired the compound in the $5.2 billion Ariad deal. Even since the FDA granted accelerated approval for the drug as a second-line treatment in 2017.
Crizotinib, the control in the trial, was the first ALK inhibitor approved and came with much acclaim. While the drug was in Phase I in the late 2000s, the stories of once-terminal patients watching their tumors shrink made for TV news fodder. But Pfizer, Novartis and Roche have all since unveiled new inhibitors that can be more effective than the first drug.
Researchers caution against comparing clinical trials too directly, but Roche’s Alecensa also showed dramatically improved progression free-survival against crizotinib in similar patient populations, bolstered by improved results in the central nervous system metastases.
Still, the drugs are not identical and, as with many cancer drugs, resistance has become a problem, with patients riding one inhibitor while it works and then going to the next. That makes each new inhibitor a potential lifeline.
“The one thing that’s clear is that each of the next-gen inhibitors have demonstrated true superiority,” Popat said. “So choosing which one is a decision between patients and their oncologists.”