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

On 18.12.2020, computer engineer @FitTuber shared @YouTube video titled "10 Safe & Useful Ayurvedic Tablets to Replace Allopathic Pills (Instant Relief)". The drugs he promoted were by @baidyanathgroup, not sure if it was paid promotion. I bought them:
https://t.co/w6Sh2pMvJf


10 drugs, details, batch numbers R given in pic👇. All by @baidyanathgroup exept 1 by https://t.co/tg46sBhJr2
We did GCMSMS, ICP-OES and FTIR analyses on these samples. Here are my 10 safer modern medicine alternatives 2 @FitTuber's untested, potentially harmful #Ayurvedic drugs


Kanthsudharak Vati by Unjha Pharma
@FitTuber: 4 sorethroat, cold, cough
Analysis: Lead 0.54 mg/kg, Cadmium 0.4 mg/kg, Thallium 0.71 mg/kg and industrial phenols.
Low values, but not ideal.

Safe alternative: Levocetrizine & non-sedative cough syrup Levodropropizine


Baidyanath Rajbati
@Fittuber: for bloating, gas
Analysis:
Mercury 1.2 mg/kg
Arsenic 2.25 mg/kg
Male anabolic hormone - hydroxy testosterone+
Curcumin
Talc powder

Safer alternative: activated charcoal+simethicone (non-absorbed, no side effects) or short course esomeprazole.


Baidyanath Bilwadi Choorna
@Fittuber - 4 diarrhoea
Analysis
Thallium 3.68 mg/kg
[fun fact: 10-15 mg/kg is lethal dose for humans. Death can occur at lower dosages] https://t.co/9ozOKROhCK
Fenretinide - synthetic anti-cancer drug
Liver toxic chromium phosph.

Safer: Racecadotril

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सत्यवती ने महर्षि भृगु से अपने तथा अपनी माता के लिए पुत्र का वरदान मांगा।ये जानकर महर्षि भृगु ने यज्ञ किया और तत्पश्चात सत्यवती और उसकी माता को अलग-अलग प्रकार के दो चरू (यज्ञ के लिए पकाया हुआ अन्न) दिए और कहा कि ऋतु स्नान के बाद तुम्हारी माता पुत्र की इच्छा लेकर पीपल का आलिंगन...

...करें और तुम भी पुत्र की इच्छा लेकर गूलर वृक्ष का आलिंगन करना। आलिंगन करने के बाद चरू का सेवन करना, इससे तुम दोनो को पुत्र प्राप्ति होगी।परंतु मां बेटी के चरू आपस में बदल जाते हैं और ये महर्षि भृगु अपनी दिव्य दृष्टि से देख लेते हैं।

भृगु ऋषि सत्यवती से कहते हैं,"पुत्री तुम्हारा और तुम्हारी माता ने एक दुसरे के चरू खा लिए हैं।इस कारण तुम्हारा पुत्र ब्राह्मण होते हुए भी क्षत्रिय सा आचरण करेगा और तुम्हारी माता का पुत्र क्षत्रिय होकर भी ब्राह्मण सा आचरण करेगा।"
इस पर सत्यवती ने भृगु ऋषि से बड़ी विनती की।


सत्यवती ने कहा,"मुझे आशीर्वाद दें कि मेरा पुत्र ब्राह्मण सा ही आचरण करे।"तब महर्षि ने उसे ये आशीर्वाद दे दिया कि उसका पुत्र ब्राह्मण सा ही आचरण करेगा किन्तु उसका पौत्र क्षत्रियों सा व्यवहार करेगा। सत्यवती का एक पुत्र हुआ जिसका नाम जम्दाग्नि था जो सप्त ऋषियों में से एक हैं।