It's Monday AM post-@ASCO #GU21 & clinic starts in a couple of hours! Lots to process - I'll try to tackle optimal 1L tx for #kidneycancer. I'll make a case for cabo/nivo, leaning on the beautiful (& timely) tables below from @lalaniMD, @SoaresAndrey & @brian_rini (1/15)

What about IO/IO? We have long f/u w #CM214 data w nivo/ipi, no doubt (@AlbigesL et al in @myESMO Open). And treatment-free interval discussed by McDermott @BIDMChealth is no doubt impt. But we've known data not as impressive for favorable risk (2/15)
And furthermore, as @ERPlimackMD points out in another tweet, impt to look at primary PD rates (seen in @lalaniMD's table) - nivo/ipi at 19%!!! CR rate used to be something we highlighted w nivo/ipi, but now comparable across studies (3/15)
Okay now to the really tough stuff - comparing TKI/IO regimens. Something interesting I will add to @brian_rini @uromigos table above is the HR for PFS by INVESTIGATOR review. If the diff in HR for PFS by IND review caught your eye, this is even more striking (4/15)
I think INV-assessed PFS is impt, but if you're a skeptic, forget that argument. Turn instead to #QOL with axi/pembro. Kudos to @brian_rini @tompowles1 @ERPlimackMD et al for advocating for QOL in KN-426. @crisbergerot et al have taughts us the importance of these metrics. (5/15)
Unfortunately, we're not seeing any improvement in QOL w axi/pembro. This is a bit concerning - if balanced between arms, are we prolonging PFS at the expense of the patient's overall well-being? Inc tumor regression should be accompanied by some symptomatic improvement. (6/15)
Okay, now on to one of the headliners at @ASCO #GU21 this past weekend. The CLEAR study presented by @motzermd @DrChoueiri @DrTHut @tompowles1 @CPRT65 et al. Simultaneously published in @NEJM - congrats friends! (7/15)
Just one point on the curves, which I heard @tompowles1 bring up on a @Uromigos podcast w @DrChoueiri (of note, I also saw @manuelmaiamd bring this up during @motzermd's presentation in the @ASCO #GU21 pres). Why do the OS curves merge? Not so in #CheckMate9ER! (8/15)
Regardless, some may be swayed by the 16% CR rate with len/pembro. Now HERE is where we need to dive into baseline characteristics. Nearly 10% more fav risk in CLEAR, and also, more pts with prior neph. So, the odds of getting CR (or even PR) stacked against #CheckMate9ER (9/15)
I'll next make the point that LEN IS HARD TO TOLERATE. I'm glad @SoaresAndrey highlights the rate of discontinuation in #CLEAR, which appears much higher than in #CheckMate9ER. I've seen 7al versions of the data, but no matter how you slice it, d/c rate⬆️with len/pembro. (10/15)
What's my experience with len? I ran a RP2 study w @DrDanielHeng @hipsytips @docjavip et al. We tried to lower dose from 18 to 14 mg & preserve efficacy, but with the caveat of this being a small non-inferiority study, it didn't appear feasible. 👀rates of d/c due to AEs! (11/15)
Remember, I was comparing 18 and 14 mg. The dose in #CLEAR even HIGHER at 20 mg! This is one of those settings where QOL data ESSENTIAL. Remember, our pts are thankfully doing better & will be on drug longer - we need to look out for their GLOBAL well-being! (12/15)
Now THIS is what we need to see. Improved QOL with cabo/nivo, as @DrChoueiri presented at #ESMO20. Remember, the dose of 40 mg is used in #CheckMate9ER - LOWER than the dose of 60 mg used in #METEOR, with cabo as 2L/3L tx. (13/15).
Confession: I was skeptical when @DrChoueiri @motzermd @tompowles1 @apolo_andrea & the brilliant team for #CheckMate9ER chose 40. But @neerajaiims & I have since reported data from #COSMIC021 (cabo/atezo across multiple settings). Efficacy at both doses seems quite good (14/15)
SUMMARY: In 2021, we are blessed w gr8 data from mult 1L trials in #kidneycancer. I feel that cabo/nivo is the way to go; the goalpost is shifted beyond just PFS/RR/OS, we now need QOL! Thx to the amazing data summaries that facilitated this thread. Open to all comments. (15/15)

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No-regret #hydrogen:
Charting early steps for H₂ infrastructure in Europe.

👉Summary of conclusions of a new study by @AgoraEW @AFRY_global @Ma_Deutsch @gnievchenko (1/17)
https://t.co/YA50FA57Em


The idea behind this study is that future hydrogen demand is highly uncertain and we don’t want to spend tens of billions of euros to repurpose a network which won’t be needed. For instance, hydrogen in ground transport is a hotly debated topic
https://t.co/RlnqDYVzpr (2/17)

Similar things can be said about heat. 40% of today’s industrial natural gas use in the EU goes to heat below 100°C and therefore is within range of electric heat pumps – whose performance factors far exceed 100%. (3/17)


Even for higher temperatures, a range of power-to-heat (PtH) options can be more energy-efficient than hydrogen and should be considered first. Available PtH technologies can cover all temperature levels needed in industrial production (e.g. electric arc furnace: 3500°C). (4/17)


In our view, hydrogen use for feedstock and chemical reactions is the only inescapable source of industrial hydrogen demand in Europe that does not lend itself to electrification. Examples include ammonia, steel, and petrochemical industries. (5/17)
this simple, counter narrative fact keeps cropping up all over the world.

hospital and ICU utilization has been and remains low this year.

it's terribly curious that so few of these monitoring tools provide historical baselines.

getting them is like pulling teeth.


we might think of this as an oversight until you see stuff like this:

this woman was arrested for filming and sharing the fact that their are empty hospitals in the UK.

that's full blown soviet. what possible honest purpose does that

this is the action of a police state and a propaganda ministry, not a well intentioned government and a public heath agency.

"we cannot let people see the truth for fear they might base their actions on real facts" is not much of a mantra for just governance.


90% full ICU sounds scary until you realize that 90-100% full is normal in flu season.

staffed ICU beds are expensive to leave empty. it's like flying with 15% of the plane empty. hospitals don't do that.

and all US hospitals are mandated to be able to flex to 120% ICU.

the US is currently at historically low ICU utilization for this time of year.

61% is "you're all going to go out of business" territory as is 66% full hospital use.

can you blame them for mining CARES act money? they'll die without it.

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Still wondering about this 🤔


save as q