I Tried It: Taselisib

Update: the morning after I posted, investigators presented SANDPIPER data in an MBC session. In response to modest benefit and AE concerns, Roche announced that they would not be pursuing an FDA submission.

Spoiler alert: check out this table presented today at ASCO.


I enrolled in a study combining taselisib with HER2-targeted therapy (T-DM1 or HP, with prior therapy on either option allowed) in metastatic breast cancer. Worth noting: PI3K mutations were not required for enrollment, in line with Genentech’s overall all-comers strategy (e.g., non-targeted atezo). My experience was not apples-to-apples with the MATCH patients, who were enrolled solely on the basis of a PI3K mutation, regardless of tumor origin. But I think it’s analagous, given that I only enrolled because of my PI3K mutation. In 2012 I had a Caris test, which was then much more exciting than it is now; so exciting that I wasn’t even mad that they depleted a five-centimeter block of tumor doing a panel of about a dozen genes plus chemosensitivity testing. We’ve come a long way in six years. Among the results was a PI3K mutation. The wonderful Dr. Cristofanilli, whose enthusiasm for targeted therapies and novel diagnostics is truly inspiring (whether he’s entirely right about their clinical relevance, it’s contagious), told me five years ago to try Afinitor in combination with Herceptin and vinorelbine. Afinitor targets mTOR, which shares a pathway with PI3K and is approved for use in hormone-positive breast cancer, in combination with Aromasin, among other indications. He recommended it over a T-DM1 trial, because he predicted, accurately, that in the near future it would be no problem to get T-DM1, though at the time it seemed like the drug would never make it to market; payer uncertainty with the off-label Afinitor was another issue (BOLERO-3 was published a couple of years later, and I imagine this would make reimbursement less of a wildcard, assuming the prescriber was willing to push for it). While I was touched that after one appointment, he would’ve gone to bat with my insurer, I went with the T-DM1 trial. There were so many next-gen PI3K inhibitors in development, and I had my eye on BKM120.

I waited. And waited. Development was apparently discontinued sometime late last year. If you look at Novartis’ 2017 annual report, BKM120 is suddenly absent from the pipeline. This was not entirely surprising, to the extent that I didn’t even see it reported anywhere, given the AEs; PI3K inhibitors are known to cause neuro issues, and the poor ER+ study subjects with their indolent cancers were up and trying to kill themselves on trial. There were also efficacy concerns. BYL719 still has a heartbeat, but I haven’t heard much about it. They’re trying it with letrozole in HR+ breast, and it seems fine.

Anyway, this story is about taselisib. I enrolled, and I lasted one week. The nausea was terrible, terrible, ondansetron every eight hours terrible, which I usually avoid because I’m so scared that if I take it, I’ll build up some kind of anti-emetic tolerance and this drug that is considered magic and the best choice we have against nausea will no longer work for me. My usual strategy against nausea is to eat candied ginger (it’s stocked with all the nuts in Whole Foods) and to lie absolutely still, which is reasonably effective. Plus my skin progressed, after a few years of relative stability, and I panicked. It just went crazy. 

ME: I feel like I did something mutagenic. That maybe the PI3K was there, but it wasn’t driving anything, and now I’ve woken it up.

DOCTOR: Yeah, that’s legitimate.

He’s the best because he tells me the truth.

Like 100% of the MATCHed patients referenced above, I was not a responder. There seems be some suspicion of the drug among physicians; my husband came home recently and said someone asked him, re: taselisib, “Does that thing even work?” 

Well. We’ve associated the efficacy of drugs targeting the mTOR pathway with hormone-positive breast because that population is pretty overwhelmingly PI3K-mutated (it may be as high as 50%). But if you look at MATCH, the mutation doesn’t really explain it. For me personally, this also isn’t the first time I’ve targeted the mTOR pathway; I’ve taken metformin since diagnosis, and if that has any anti-cancer activity, it’s along this pathway, and I definitely haven’t associated it with rapid PD. 

I haven’t written about my taselisib experience because I really don’t know what to make of it; it’s disappointing, and I don’t want this blog to be a series of lame anecdotes, because oncology is a thrill to me in ways that are separate from my own case. While I want to be honest about what happens to me, it’s a lens and not the thing itself. So when I see that I join the 0% of MATCH patients who were PI3K mutated and yet taselisib non-responders, there is some relief that I’m not going to be the one to be a black mark on this drug (I did ask my doctor if I would be on the record as non-evaluable, because I progressed halfway through the first cycle, or as a PD, and I don’t actually know what happened), but I also want us to believe in genomics until something better comes along. Maybe PI3K is just not an ALK, or, in ASCO 2018 terms, a RET.  It’s not like chemo works so great. We can do better than that, right?

Make $$$ [for your doctor] from home!

There’s so much waste in U.S. cancer care that any pet issue represents but a drop in the proverbial bucket, but here’s one of mine: physicians don’t push self-administration of GSCFs like Neulasta because they can bill the in-office delivery of the drug as an outpatient procedure. So instead of faxing a prescription to a specialty pharmacy to have a box of pre-filled syringes delivered to the patient’s house, which would be charged exclusively under the patient’s pharmacy benefits, the physician/center will have the patient return for a separate appointment after chemo to have a simple subcutaneous injection billed as a medical benefit. Even medical staff aren’t consistently aware that home administration is an option; a nurse once asked after a dose of Abraxane if I had an appointment for Neulasta for the next day, and I told her I’d be giving it myself at home. She raised her eyebrows and said, “Do you have someone at your house that can give injections?”

It’s a subcutaneous injection. You cannot do it wrong. Continue reading “Make $$$ [for your doctor] from home!”

EXEL’s trash, Kadmon’s treasure? 10+ years with tesevatinib

Three years ago, I learned of KD-019, an EGFR-inhibiting wonder TKI for which there just happened be a study enrolling, right at the mid-tier academic institution/portal to hell in which I was currently sitting. I nodded along appreciatively to phrases like better than Tykerb! while thinking, Kadmon. Kadmon. Oh, right, the one where the CEO just got out of prison.

Continue reading “EXEL’s trash, Kadmon’s treasure? 10+ years with tesevatinib”

The Puma Panel

I didn’t think neratinib was getting through. As much as I want more flexibility in prescribing and a more moderate drug approval pathway, why does it have to be neratinib?

Despite very modest clinical benefit, a lot of toxicity and a broad label, this morning’s FDA panel voted 12-4 in favor of more options for cancer patients. The panelists did seem to take patient selection seriously, though it’s unclear how that will pan out when Puma is loose in the market. What I’m curious about is whether patients will demand it, whether the patient representatives Puma paid to speak – the what-if-Mommy-dies, I-want-to-do-everything-to-fight-this types – are representative of the overall population. Continue reading “The Puma Panel”

New Threat: “Patient-Dictated” Care

While we’ve been worrying about nuclear war and rising global fascism, a post on KevinMD last week reminded us of a persistent and no less real danger: patients who ask for shit. The blog’s author draws a line between “patient-centered care” and “patient-dictated care”, the latter of which entails the physician sighing mightily yet rolling over at any patient request. What choice does he have, really? He’s just trying to keep the lights on in this crazy world.

The example given is antibiotic abuse, that old workhorse – just as scary and describable as it was in that 60 Minutes episode back in 1998. Can You Believe this Asshole Wants Antibiotics for a Cold?! has been kicking around at least since I was in high school, and despite its wear, it won’t die as the catchall justification for why physicians must remain the keepers of the knowledge. They are the rare, anointed ones, elevated by the combination of intellectual superiority and moral purity; they alone understand the dangers of antibiotic resistance. Continue reading “New Threat: “Patient-Dictated” Care”

Liquid Biopsy Continues to Disappoint

Confession: I have been burned by Guardant twice. Both times were my fault, the first on account of my wide-eyed idealism and the other because I didn’t stick to my guns when it counted, but this has seeded a personal and possibly misdirected venom toward the company.

It helps that the product sucks. Continue reading “Liquid Biopsy Continues to Disappoint”

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. Continue reading “Puma Post-APHINITY”