Puma Post-APHINITY

Puma presented at Cowen today, and I listened to the webcast hoping for a reaction to APHINITY, but alas, they kept Q&A to the breakout session. The tone of the presentation did seem a little grim, but between the crushing of adjuvant dreams and half the slides being devoted to unmanageable diarrhea, I guess it was always going to play grim.

There wasn’t much in the slides that was new, but I continue to be baffled by Puma’s view on their market size. Who are these clinicians promising to prescribe neratinib to every patient who walks through the door? This is not another Herceptin. Herceptin mythology aside, the drug works. It works alone and with minimal side effects. Though we haven’t seen APHINITY numbers, I’m guessing adjuvant Perjeta + Herceptin is a done deal. And yet Puma’s invoking Herceptin sales to demonstrate the adjuvant opportunity. Herceptin! This drug is a Tykerb at best. Puma did spend some talking about the metastatic setting, which is smart because it’s the only setting where neratinib may have a chance of being prescribed, but their combos are bugging me: swapping out Tykerb for neratinib in Tykerb/Xeloda, for example. Who in the U.S. is dropping Herceptin in metastatic patients to give Tykerb/Xeloda alone? It’s always Herceptin/Tykerb/Xeloda in this population, even if that’s not the label. Puma is running a neratinib/Xeloda vs. Tykerb/Xeloda head-to-head study, but I have no idea how they’re getting patients to enroll. (Well. I have an idea.)

On the subject of Tykerb, the presentation summoned up data showing a reduced risk of brain mets in patients treated with neratinib, suggesting that there could be a role here for the prevention of these mets. Even if the benefit checks out upon publication of these data, that doesn’t mean it will have any clinical impact. Doctors are not innovators. Treatment paradigms are generally cautious and conservative, and I’ve been surprised by the reluctance with which oncologists prescribe anything. People think cancer patients have drugs thrown at them without a second thought, and this hasn’t been my experience. Toxicity is a huge issue to every oncologist I’ve met, from people practicing at high-volume academic centers to solo community practitioners. They do not want their patients to be sick or in pain. You would expect this MD population to be chill about mounting toxicities, but I’ve never seen evidence of that. I’ve left practices because I felt there was too much emphasis on QOL and not enough on outcomes. An MD I trust and admire has been telling me for three years that I’m “not sick enough” to try a PD-L1 inhibitor, because there can be awful and unpredictable side effects. Tykerb has few AEs, passes the BBB and is widely available, so if anyone had any intention of implementing CNS mets prophylaxis, it would have happened already. No one prescribes Tykerb for this purpose, and that won’t change for neratinib.

Thanks, but no thanks, neratinib. We’ll see this summer if the FDA agrees.

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