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)

More from Health

You May Also Like

THE MEANING, SIGNIFICANCE AND HISTORY OF SWASTIK

The Swastik is a geometrical figure and an ancient religious icon. Swastik has been Sanatan Dharma’s symbol of auspiciousness – mangalya since time immemorial.


The name swastika comes from Sanskrit (Devanagari: स्वस्तिक, pronounced: swastik) &denotes “conducive to wellbeing or auspicious”.
The word Swastik has a definite etymological origin in Sanskrit. It is derived from the roots su – meaning “well or auspicious” & as meaning “being”.


"सु अस्ति येन तत स्वस्तिकं"
Swastik is de symbol through which everything auspicios occurs

Scholars believe word’s origin in Vedas,known as Swasti mantra;

"🕉स्वस्ति ना इन्द्रो वृधश्रवाहा
स्वस्ति ना पूषा विश्ववेदाहा
स्वस्तिनास्तरक्ष्यो अरिश्तनेमिही
स्वस्तिनो बृहस्पतिर्दधातु"


It translates to," O famed Indra, redeem us. O Pusha, the beholder of all knowledge, redeem us. Redeem us O Garudji, of limitless speed and O Bruhaspati, redeem us".

SWASTIK’s COSMIC ORIGIN

The Swastika represents the living creation in the whole Cosmos.


Hindu astronomers divide the ecliptic circle of cosmos in 27 divisions called
https://t.co/sLeuV1R2eQ this manner a cross forms in 4 directions in the celestial sky. At centre of this cross is Dhruva(Polestar). In a line from Dhruva, the stars known as Saptarishi can be observed.
The UN just voted to condemn Israel 9 times, and the rest of the world 0.

View the resolutions and voting results here:

The resolution titled "The occupied Syrian Golan," which condemns Israel for "repressive measures" against Syrian citizens in the Golan Heights, was adopted by a vote of 151 - 2 - 14.

Israel and the U.S. voted 'No'
https://t.co/HoO7oz0dwr


The resolution titled "Israeli practices affecting the human rights of the Palestinian people..." was adopted by a vote of 153 - 6 - 9.

Australia, Canada, Israel, Marshall Islands, Micronesia, and the U.S. voted 'No' https://t.co/1Ntpi7Vqab


The resolution titled "Israeli settlements in the Occupied Palestinian Territory, including East Jerusalem, and the occupied Syrian Golan" was adopted by a vote of 153 – 5 – 10.

Canada, Israel, Marshall Islands, Micronesia, and the U.S. voted 'No'
https://t.co/REumYgyRuF


The resolution titled "Applicability of the Geneva Convention... to the
Occupied Palestinian Territory..." was adopted by a vote of 154 - 5 - 8.

Canada, Israel, Marshall Islands, Micronesia, and the U.S. voted 'No'
https://t.co/xDAeS9K1kW