Little tucatinib is all grown up! The TKI that started out at Array long, long ago has now been FDA approved in combination with Herceptin and Xeloda for the treatment of 2L+ HER2+ metastatic breast cancer. Additional international approvals could be imminent, as the submission was part of a concurrent review program between the FDA and worldwide regulatory authorities. This is fantastic news for everyone but the Kadcyla sales force, though Genentech will get a slice of the pie via some incremental Xeloda sales.
The approval was supported by data from the HER2CLIMB trial, which enrolled 612 subjects and randomized them 2:1 to tucatinib or placebo plus Herceptin and Xeloda. Subjects with brain mets at baseline comprised 47.5% of the study population. This is their story:
Among subjects with measurable disease at baseline, the confirmed objective response 40.6% in the tucatinib group and 22.8% in the placebo group. But look at those numbers! The brain mets patients didn’t do much worse than patients with visceral mets. Cascadian went in boldly by enrolling brain mets patients, and the gamble paid off. They have brain mets featured prominently in their labeling, and they’re an example for all the companies that have excluded brain mets patients from their trials for fear of muting response rates. But patients in the real world, in HER2+ breast cancer, have brain mets. I have brain mets. I’ve looked at a lot of eligibility criteria, and while we’ve seen brain mets exclusions gradually relax over the past decade, most trials that allow them still caution that they must be stable.
Joining DS-8201 as a likely FDA approval in early 2020 is tucatinib, a HER2-targeted small molecule TKI that I’ve been fangirling for years. If this keeps up, I’m going to be able to treat my cancer with actual new medicine and not just mental fortitude.
Not to malign the Herceptin-plus-X paradigm that’s bridged me all this time, but it’s been a while since the T-DM1 and Perjeta launches of 2013. In metastatic cancer years, it’s a real long while.
Onto the successes of HER2CLIMB, Cascadian Therapeutics’ (now Seattle Genetics’) phase III trial comparing tucatinib + Herceptin + Xeloda to placebo + Herceptin + Xeloda. The trial enrolled 612 subjects and was randomized 2:1, and subjects had been previously treated with Herceptin, Perjeta and T-DM1. The press release notes that 47% of subjects had brain mets at the time of enrollment. A classic placebo-controlled RCT in a tough crowd? Yes, please. What’s not to like about these guys?
We don’t know a lot yet, with actual numbers to be presented at San Antonio. But to pull the highlights from the press release:
Tucatinib + H/Xeloda combo met its primary PFS endpoint, with a 46% reduction in risk of PD or death compared to placebo + H/Xeloda
Among secondary endpoints, OS was superior for the tucatinib arm versus placebo + H/Xeloda, with a 34% reduction in risk of death
For patients with brain mets at baseline, tucatinib + H/Xeloda offered a 52 percent reduction in the risk of PD or death compared to placebo + H/Xeloda