Fiona Blackhall, MD, PhD

FORMAL STUDY discussant, Fiona Blackhall, MD, PhD, of the University of Manchester, UK, welcomed brigatinib (Alunbrig) as a new first-line option for ALK-positive patients but said, “In the absence of comparisons of next-generation ALK inhibitors, it will take some time to determine if there is indeed a best ALK inhibitor for our patients.”

There are three approved treatments for ALK-positive NSCLC: crizotinib (Xalkori), ceritinib (Zykadia), and alectinib (Alecensa). “Of these treatments, the National Comprehensive Cancer Network® (NCCN®) prefers alectinib, the only next-generation ALK inhibitor, compared with crizotinib. Now we have a fourth: brigatinib. The question is which would we choose in the clinic,” Dr. Blackhall said.

The Next Chapter: After Second-Line Treatment

“WITH SHORTER follow-up at present, we don’t know if brigatinib can beat the progression-free survival seen with alectinib seen in the ALEX trial. It is not possible to determine if brigatinib has better intracranial effects than alectinib,” she continued.

“Both brigatinib and alectinib are better tolerated than crizotinib. But it might be just as good to start with crizotinib in patients with no brain metastasis and then use a second-generation inhibitor at disease progression. We don’t have prospective randomized data on this,” Dr. Blackhall noted. “It is also frustrating that we don’t have translational information on the spectrum of mutations at disease progression following a second-generation ALK inhibitor such as brigatinib or alectinib used in the first-line setting. The next chapter will be working out what to use to treat our patients after treatment with a second-generation ALK inhibitor either first or second line,” she said.

A research project called the ALK Master Protocol, being developed by the National Cancer Institute, and led by Alice Shaw, MD, of Massachusetts General Hospital, will enroll patients treated with next-generation ALK inhibitors for genotyping to enroll into a treatment according to genotype. This effort will help guide decisions in the future, she said. ■

DISCLOSURE: Dr. Blackhall has received research funding from AstraZeneca, Novartis, Pfizer, and Amgen; is on the advisory board of Regeneron, Medivation, Abbvie, Takeda, and Roche; is a consultant with CellMedica and MSD; and is on the speakers bureau of Boehringer Ingelheim.