MKawMD

@ArndtVogel @Esmo Why right target? I do not see any argument from this data that would support CLDN18.2 as plausible target in PDAC.

Zolbetuximab plus gemcitabine and nab-paclitaxel in CLDN18.2+ metastatic PDAC: phase II GLEAM study @ESMO-GI 👉Primary endpoint not met, no OS & PFS benefit 👉Toxicity manageable 🧐Not the right drug, but maybe the right target

@Banana_Oncology 6 month PFS in 2nd line - impressive!

$RVMD Zoldon+Darax 50% ORR in 2L PDAC. One G5 TRAE (1/60) though

@Banana_Oncology GnP is not rough. Casual chemo. Winning KRASi race might be tied not to efficacy, but tolerability. My guess is that in P3 trials there will be tendency to shorten/skip chemo when given with KRASi. Questions on long-term impact of this - have to wait for the data.

$RVMD Zoldon+Chemo 61-82% ORR in 1L PDAC, very impressive efficacy signal! 61-80% G3+ TRAE seems high, but we know GnP is rough

@krzysztoflosin O odległy rokowaniu decyduje przede wszystkim typ nowotworu złośliwego oraz jego stopień zaawansowania. Nie da sie na to pytanie odpowiedzieć bez doprecyzowania tych danych.

@AgnieszkaSzust3 Mam pytanie. Osoba z immunologiczna choroba gdy otrzyma diagnozę raka przy dzisiejszym leczeniu o ile procent mniej szans przezycia 5 lat ma czy nie ma takich wyliczeń? Bo jednak teraz często gęsto jest immunoterapia

Short🧶Naprawdę dobre wieści dotyczące leczenia raka trzustki - po raz pierwszy od dekad coś naprawdę działa. Rak trzustki od lat jest jednym z najbardziej bezlitosnych nowotworów. Po diagnozie większość pacjentów nie dożywa roku. Skuteczne terapie były przez dekady niemal

@AgnieszkaSzust3 @krzysztoflosin Przepraszam, ale to selection bias. Dlaczego? Bo nikt nie poda immunoterapii choremu z AIH, PSC czy aktywnym Leśniewskim. W analizie retorspektywnej eksponowano głównie chorych na łuszczyce czy RZS. O ile przy łuszczycy nie mam obaw, o tyle z RZS mam złe doświadczenia.

@krzysztoflosin Duże badanie JAMA Oncology (2022, n=1822 pacjentów, 18 typów nowotworów) wykazało: nie ma istotnej różnicy w całkowitym przeżyciu między grupą z chorobą autoimmunologiczną a bez, przy założeniu, że immunoterapia została podana i pacjent był monitorowany. jamanetwork.com/journals/jamao…

@5_utr Sometimes the gain is small or obsolete. But acting like systemic treatment is not working at all is... poor science. And dumb.

@5_utr The game starts when one starts to see all modalities aimed at one direction. Radical NSCLC? Poor results without neo/adjuvant IO. PDAC? Chemo boost long term survival after surgery 5 fold. LGG? Adding PCV gains >5 years on average.

Name a common solid tumor cured by drugs alone. I’ll wait. The oncology world is drunk on vaccines, pills, and infusions. Surgery and radiation are quietly doing the work nobody celebrates. The math is unambiguous. The narrative is embarrassing. Thread. 🧵

@5_utr Yeah, sure. Like blocking BCR-ABL or HER2 does not work. Repeating the same arguments over and over does not make You right.

The oncogene addiction hypothesis is empirically bankrupt. Oncology has industrialized false hope, but this drug too is doomed to fail. The field rewards hype and punishes skepticism. Patients pay the price. I will enjoy being right.

@5_utr Go read for whom and when ESMO endorse GCPs - they have whole paper on that. And then please provide how many of patients included in analysis meet guidelines recommendation. My guess - 5%? If so, does this really adress the issue?

@MKaw13 “Check societal guidelines.” The NCCN recommends CGP for nearly every advanced solid tumor. ESMO endorses it. CMS reimburses it. The guidelines ARE the overclaim. Citing the guidelines as the defense for the guidelines is circular reasoning

‼️ Bayesian horseshoe survival model on pan-cancer data: 10,170 patients, 33 cancer types, 142 oncogenes, 2,996 deaths (29.5%). Full adjustment for cancer type, stage & age. Results are beyond brutal for precision oncology. Let’s go! 🧵

@5_utr No argument, keep the same repetition. Sorry, the paper does not provide good argument against GCPs due to underlying flaws. Won't convince You, You won't convince me, but at least the audience have some more perspective.

@MKaw13 First it was poor science. Then not shocking. Then argumentum ad infinitum. Now argumentum inane. The Latin keeps escalating as the argument keeps shrinking. Meanwhile the horseshoe prior said the same thing in one line of Stan code and didn’t charge $5,000 for the privilege.

@5_utr Argumentum inane. There will be no common denominator, as per current understanding of cancer, for seminoma, myeloma and SFT. If one search for it, than one is a fool. And nor FM, nor NCI, nor NCCN state that CGPs would be one. CGP are a tool, not a way of salvation. Simple tool.

@MKaw13 “Not shocking” — then why does Foundation Medicine charge $5,000 to look for the common denominator you just admitted doesn’t exist? Why did NCI fund the MATCH trial across 40 tumor types? Why does every NCCN guideline recommend CGP? Someone is shocked. Follow the money.

@5_utr Stop the cherry-picking lad. Writing about PDAC and then You try to extrapolate my argument on whole field. Argumentum ad infinitum. Check societal guidelines on who should get CGPs. Only few patient groups get this recommended as SOC.

@MKaw13 “Never heard a physician say CGPs would save anyone.” Beautiful. So 1.5 million panels ordered annually, zero physicians claiming benefit, zero survival signal in 10,170 patients. We’re all in violent agreement and somehow the panels keep getting ordered. Follow. The. Money.

@5_utr Seeing numerous PDAC patients per week. Never heard of any who told them CGPs would save anybody, with most of physicians arguing against it in all cases. The industry built many dead ends, CGPs are not biggest (look at protons dear RadOnc!).

@MKaw13 “CGPs are useful as a tool and only a tool.” Correct. A stethoscope is a tool. Nobody built a $50B industry on it, ran 4000 biomarker-selected trials with it, or told stage IV pancreatic ca patients it would save them. The tool isn’t the problem. The religion built around it is.

@5_utr Expecting similar effect on any prognostic factor among multiple oncological scenarios remains flaw. Putting seminoma, melanoma, myeloma and solitary fibrous tumors and being supprised of not finding any common denominator other than stage and type of cancers is not shocking ;)

@MKaw13 Started: “poor science to mix cancers.” Ended: “gene effects can’t be extrapolated across cancers.” You’ve traveled the entire length of our argument to land on my conclusion, fighting the whole way. The horseshoe prior got there faster and with less typos 😜

@5_utr Still, many arguments later, I do not agree that Your paper support this conclusions properly. Virchow already won prior to Your work. Cheers for him. And cheers for You for paper, with all good and bad sides.

@MKaw13 70 years. Trillions of dollars. Millions of tumor biopsies. Thousands of biomarker-selected trials. And stage — something Virchow knew in 1858 — still explains 49% of survival variance while your oncogenes explain ~0%. The last 70 years called. They want a refund.

@5_utr Beside - CGPs *are* usefull in certain circumstances. As a tool and only tool. Any tool can be used improperly.

@5_utr As said previously - despite the fact that I do agree, I do not find Your paper to be providing valid reasons against CGPs.

@5_utr Mixing completely different clinical scenarios with completely different treatment option and prognosis is not a way of detecting prognositc factor. Withing cohort in cohort - as with KRAS in PDAC - You will find prognostic factors that *cannot* be extrapolated for all cancers.

@MKaw13 Notice the goalposts: started with “mixing cancers is poor science,” now it’s “look at specific KRAS mutations in PDAC specifically.” Every time the data says no, the hypothesis gets smaller. That’s not refinement. That’s a retreating theory protecting itself from falsification.

@5_utr Define rather homogenous population in terms of prognosis. Seek for prognostic factors. Understand how this might be explained. Seek for plausible way of interfering with this. Test this in this population. Then try to extrapolate. Yeah, this is last 70 years of oncology.

@MKaw13 So your proposed method is: exclude cancers where genes won’t show signal, then declare genes show signal in the remainder. Congratulations, you’ve just described 30 years of precision oncology trial design.