DS-8201 has a PDUFA Date

Yes! The date is F1Q:20, so I might be getting a prolonged OS for Christmas!


Daiichi announced today that they’ve been granted FDA Priority Review for their highly worthy DS-8201, which looked promising out of the gate and recently demonstrated a 59.5% response rate in HER2+ metastatic breast cancer patients who had previously been treated with T-DM1. Those results, from a 118-subject Phase 1, were published in June. The study also reported some total insanity, like a 20.7-month duration of response (DOR) and a 22.1-month PFS. It’s not comparable given the phases, designs and number of subjects enrolled in this phase 1 versus EMILIA, but T-DM1 had a phase III PFS of around 9-10 months, so DS-8201 is likely to displace that agent as the second-line treatment of choice in this setting (first-line being taxane + Herceptin + Perjeta).

The data above are old news, but the press release says the submission package also includes pivotal phase 2 DESTINY-Breast01 data, which “validated” the phase 1 results and which no one has seen yet, though they note that it will be presented at San Antonio. DESTINY 1 looks at a similar population (T-DM1 pre-treated MBC), but its 230 subjects were randomized to varying dose levels. Primary endpoint is ORR, so it would be shocking if this result isn’t pretty compelling, considering what we’ve seen so far. 

Like T-DM1, DS-8201 is an ADC where Herceptin is conjugated to a chemo agent; in DS-8201’s case, it’s a TOP-I inhibitor, similar to irinotecan.

Where did we leave off?

Was it the brain mets? We’ll start with the brain mets.

There were a bunch of them. A dozen? A couple were giant. I had whole brain radiation, which I always swore I wouldn’t do out of fear of cognitive decline. Six months out, I can still tie my shoes and spell my name, so I guess it’s turning out fine. 


When the WBR was over, I did what any reasonable person with no access to tucatinib and looking to avoid the Maintenance Nerlynx would do: I hopped on a plane to Germany. (Before you judge me for my rash leap to dangerous, unproven treatments administered in rogue foreign clinics, rake Pubmed for some rigorous efficacy data on FDA-approved brain mets interventions. I’ll wait.) 

One of the reasons I was excited to come back to the blog was so I could tell this story. My German doctor almost made me cry the day I met him, in the most unexpected way.

He was walking me through treatment options in his office, some EMA-licensed, some not, many occupying a regulatory gray area for which we don’t really have a U.S. analogue. The rules around the manufacture and administration of these treatments seemed a little vague, and my worry was that the treatments themselves would end up supply-constrained (what would be more frustrating than having one dose of a treatment and then never being able to secure a follow-up dose?), or that the clinic itself would be shuttered for some nonsense violation, and I’d lose access that way. Note that I wasn’t worried about safety, which is a fun consequence of the brain mets. What can hurt me now but being afraid?

My doctor assured me that it wouldn’t be a problem. He elaborated, and some of this (particularly the legal circumstances and terminology) may have been lost in translation, but the gist of it was this:

There was a court case in Germany where a physician was charged with murder for falsifying lab results and other medical records for a patient in need of an organ transplant, making the patient appear sicker than he was. For this reason, the patient was moved up the transplant list and received the transplant while other patients awaiting organs died. The falsified documentation was uncovered, and the physician was charged and found guilty. On appeal, a higher court reversed the judgment, deciding that the doctor was responsible for his patient, not every sick person in Germany.  This set a precedent that gave physicians a lot of latitude in patient care. He’d go on to add that it applied to unproven or unlicensed therapies if the doctor determined that the benefits outweighed the risks, which he made evident to me was a pretty low bar given the brain mets.    

All I heard, loud and clear, was My only obligation is to you.

I almost burst into tears. What is this blog other than the hope that a doctor would say those words to me? I love trashing scummy companies as much as anybody, but why would any of this bother me so much if I weren’t clinging to that ideal? In that office, suddenly, my guard was down and I relaxed; I would try anything, pay anything, keep any secret, now and later and long after I’m gone (let my husband deal with that one; tell them the nachtkrapp got me), because for once the transparency existed where it mattered and not where it didn’t.

U.S. healthcare is programmed so this scene would never happen, and I would argue that the cost of that is trust. The physician-patient relationship is not a partnership, and it won’t be as long as we continue to cloak the reality that your doctor doesn’t always want what you want. This was not my first experience with ex-U.S. care, and I’m conflicted about those experiences; in the EU I received in many respects higher-quality, more pragmatic care than I could dream of in the U.S., but there was also some great frustration that an American adult who grew up in the candy store of U.S. healthcare can probably never reconcile. But that conversation, in that German clinic, was the clearest validation I’ve seen that the ideal is possible. It can be done. This is how you empower a patient.