Medical Director, LCC Cancer Center | Honest, data-first oncology trial analysis (PFS ≠ OS). Community practice perspective.

New Jersey, USA
Joined February 2010
The metabolically healthy obese folks are real, no argument there. But the “you literally can’t get diabetes without the genes” part isnt accurate. Even in the lowest genetic-risk groups, obesity still increases diabetes risk several fold compared to lean people with the same scores. There’s no zero risk group where weight doesn’t matter.
Replying to @DrIronJunkie
You cannot get diabetes even if you are overweight and don't have the genes. We have 500-pound patients that can't get on GLP-1s because their A1C is too low and they're not diabetic. You can argue that if you have the underlying genetics and you gain weight and are overweight, then you display diabetes or become diabetic. Sure but you must have the underlying genes.
202
Noah Lindenberg, MD Oncologist-Hematologist retweeted
Replying to @nlindenberg
I fall asleep when I see a blue background with yellow text. 😬 I am pretty sure we had this debate when PowerPoint first came up. It was probably considered “lazy” and boring to use PowerPoint slides and “true” scientists were supposed to use hand-written slides or maybe draw diagrams with chalk! AI is a new technology and whether we like it or not everybody is going to use AI for slides in couple of years. Everybody! We are just going to get better at this. And instead of spreading shame and humiliation on those who use AI for presentations we need to organize a webinar and lectures on how to use AI for academic presentations. In academia, if we see someone making a mistake, we should not point fingers; we should give a hand of support so we can grow together! Same as we learned how to use PowerPoint we are going to learn how to use AI better for slides. Ironically, one of the first tweets in this debate used AI to generate a picture to make fun of and humiliate a colleague making a presentation. So it’s ok to use AI but not for the academic lectures!
1
1
4
471
So it’s not really about the speaker doing the work, it’s about who’s helping. That’s a different argument from your first post. If influence on content is the concern, I’d worry a lot more about the pharma slide authors. Shaping the content is literally the job. AI working off a speakers outline and data isn’t trying to sell anything. Agree effort matters, but the effort that makes a talk good is reading the papers and figuring out what you think. If it were building the slides then every fellow made deck would be a bad talk, and plenty of them are great. Either way the speaker owns what’s on the screen, we agree on that
Fellows are human. CME employees are human. Pharma med writers are human. AI is not. AI-made slides don’t just mean boring, repetitive graphics. They can influence the content too. Crafting slides takes time and effort. But that effort is often what makes a presentation great.
312
Fellows have been making attendings’ slides forever. Same with med ed companies and CME slides, and pharma talks are sponsor slides you’re not even allowed to change. Never heard anyone call that a ❌ And if I give AI my outline and my data and then rewrite half of what it makes, which emoji is that? Honestly the ✅ worries me more. “Polish and enhance” is how a wrong HR ends up on a slide. Nobody’s layout ever made up a p-value. We’re letting AI scribes write chart notes now. Slides seem like an odd place to take a stand. Also the post you’re quoting used AI for the punchline 🙂 What matters is whether the speaker knows the data and checked the numbers, not who made the slides.
Being invited to give a lecture should always be considered both an honor and a responsibility. One that should not be handed over to a machine. ❌ Having AI create your slides for you ✅ Using AI selectively to polish and enhance human-generated content
6
1
18
9,946
36 mo median OS with RT then IT trastuzumab/pertuzumab for HER2+ leptomeningeal disease (Moffitt, ESMO 2026). We used to quote 4-5 mo for this, so it's a big number. The comparison deserves a closer look.
1
1
287
The 4.4 mo control is MD Anderson 1997-2012, before T-DXd and tucatinib, and it counts from diagnosis, so it includes pts who died within weeks. This trial needed pts well enough for an Ommaya. A 2005-2019 Toronto cohort already had a median of 15.4 mo for HER2+.
1
97
Still, 36 mo is well above the earlier IT trastuzumab trials at around 8-10 mo, so selection may not explain all of it. Pts could stay on T-DXd, so I'd want to know how many did. The trial we need is modern systemic therapy with or without the IT drugs, randomized.
78
Disagree. The AI "slop" likely was poor human oversight/prompting. Used properly AI is incredible helpful research tool.
I recommended rejection for a paper that was, in my opinion, AI slop in both content and style. I was satisfied the editorial decision was for rejection, but it concerns me is that none of the other reviewers seemed to find problematic the AI-typical rhetoric. I don’t want to punish AI use automatically, and, indeed, I use AI in some of my own writing. The ideas content should be evaluated for what they’re worth. But in persuasive or semi-persuasive writing like position statements/perspectives (which this was), narrative reviews, or discussions of research articles, I do think reviewers/readers ought to be on the lookout for typical, whole-cloth AI writing that is super slick. I’m talking about out-of-the-box default model output that is unedited by human and scores 100% on Pangram. It can dress up vacuous claims and poor logic trains with vague clickbait statements and sales-pitch verbiage that inflates the importance of the supporting evidence. You see it all over LinkedIn and it’s begun to infiltrate scholarly journals. Editorial norms are still forming on this issue. What do you think?
2
9
2,506
This one bothers me. When SAFFRON opened in Aug 2022 there was real equipoise, savo + osi only had single arm data and chemo was the post-osi standard. That changed in June 2025 when SACHI, a randomized phase 3 of the same combo, showed a big PFS benefit over chemo and China approved it. I can see the case for SAFFRON continuing to randomize, SACHI was China only and mostly after 1st or 2nd gen TKIs. I can't see the case for still denying chemo pts the combo once they progressed. Every one of them got in because a biopsy showed MET-driven resistance, and outside China savo was essentially unavailable. That includes pts randomized before June 2025 who progressed after it. SACHI, same combo and same PI, let chemo pts cross over and 43% did. KRYSTAL-12 allowed crossover to adagrasib, and GEOMETRY-E, capmatinib + osi in this same setting, added it by amendment. No SAFFRON amendment adding crossover has been reported, and that likely made the OS gap bigger than it would have been with MET-directed therapy available after chemo.
1
214
Pan tumor off one positive ph3 outside lung, from one country, at an interim? GI1 is a real result, first ph3 to beat an active PD-L1 arm on OS in BTC. But there was no PD-L1 plus bev arm, so we don't know yet what the bispecific itself adds. EA2251 should tell us.
Ivonescimab is the next pan tumor blockbuster drug . Full stop . @OncBrothers @OncoAlert @myESMO #ESMO26 @JacobPlieth
2
199
Nice work by Dr. Powles and the VOLGA team. Durva/EV improved OS with EV given only before cystectomy, which makes sense for pts who struggle after surgery. I'd like to see EFS events by type in each arm, since 21% of controls never had surgery vs 15% on durva/EV.
Presented at #ESMO26: In patients with muscle-invasive bladder cancer, event-free survival at 24 months was 63.5% with perioperative durvalumab plus neoadjuvant enfortumab vedotin as compared with 45.1% with surgery alone. Full phase 3 VOLGA trial results: nej.md/4z7dQFm @myESMO
1
2
274
DeLLphi-305 is a real OS win, HR 0.42, and since many SCLC pts never reach 2L, giving tarla early makes sense. But only 33 of 281 control pts got tarla later, so the trial can’t tell us how much of the gain is early tarla vs any tarla at all.
Presented at #ESMO26: In a prespecified interim analysis of a phase 3 trial involving patients with extensive-stage SCLC, the median overall survival was 21.1 months with tarlatamab–durvalumab maintenance therapy and 12.7 months with durvalumab alone. Full DeLLphi-305 trial results: nej.md/4iveIgW @myESMO
2
7
311
LITESPARK-012 is consistent with KEYMAKER-U03, where qmab/pembro/len had numerically lower ORR (71.3% vs 80.6%) and median PFS (18.0 vs 26.3 mo) than pembro/len. It adds anti-CTLA-4 to a PD-1/VEGF TKI doublet, a different question from ipi with nivo, which 8Y8 tests.
LITESPARK-12 tested Len/pem/CTLA4 vs Len/pem in 1st line advanced RCC. This, and the adjuvant nivo vs ipi/nivo trials both add CTLA4 to Nivo. #ESMO26 8Y8 (ipi/nivo vs Nivo) is long awaited. Uncertainty on the role of CTLA4 is increasingly uncertain @brian_rini @DrChoueiri @OncoAlert
2
2
254
I agree these are impressive results. One apparent correction, though, since these numbers are being shared widely. The HR 0.66 you quoted is from the first-line patients only, nivo/ipi vs nivo alone. That comparison wasn't statistically significant: p was 0.043, and the trial needed p below 0.006. The OS result that was significant vs nivo alone is the one on the slide you posted. It includes patients treated in any line (about 40% had prior therapy for metastatic disease): HR 0.61, five-year OS 74% vs 62%. In first-line patients, the trial clearly shows nivo/ipi beats chemo on OS (HR 0.37, even though most chemo patients later got immunotherapy). It doesn't prove that adding ipi beats nivo alone; first-line PFS vs nivo also fell short of significance. That matters because ipi adds toxicity. Across all lines, grade 3-4 treatment-related side effects were 22% vs 14%, and adrenal insufficiency (any grade) was about 10% vs 3-5%, usually permanent. Agree chemo alone has no first-line role outside a true contraindication to IO, with one caveat: confirm the MSI result. In the first-line part of 8HW, 16% of patients called MSI-H locally weren't confirmed centrally, and the ones who turned out to be MSS/pMMR had a median PFS under 2 months on nivo/ipi (small numbers). Agree duration of therapy and oligoprogression are the next questions that are often neglected in ICI trials.
For the final act of CheckMate 8HW, we finally have the significant OS data the doubters have been asking for. What happens when you have a great treatment and an even better one for a study (and almost everyone crosses over)? You have to wait a really, really long time for OS. Also, some thoughts on splitting the alpha I won’t get into here. Nivo/ipi vs nivo alone vs chemo, MSI-H/dMMR mCRC. Final OS analysis. Response rate 72% with nivo/ipi, 58% with nivo alone. 
Median OS still not reached. 
OS HR 0.66 for nivo/ipi over nivo, statistically significant. 
77% of nivo/ipi patients alive at 5 years. Three out of four patients alive at five years. In metastatic colorectal cancer. 🤯 Not even going to talk about the chemo arm. It's clearly worse, and there is never a time to give chemo in MSI-H unless someone has extreme, active autoimmune disease. “Debulking” is absolute nonsense. Bottom line: the doubters got their OS. Nivo/ipi is the first-line standard for MSI-H mCRC. Next steps: how do we decide length of therapy, and how do we manage oligometastatic progression? #ESMO26
@OncoAlert @TheGutOncLab @OncoAlert
1
270
One caveat on ‘SoC’: the control arm got no pembro, which most PD-L1 CPS ≥1 US patients would get. In the PD-L1+ (TAP ≥1) subgroup, the triplet’s OS gain wasn’t significant (HR 0.82; exploratory). No head-to-head data vs pembro + trastuzumab + chemo.
Replying to @OncBrothers
5. HERIZON-GEA-01: Zanidatamab ± tislelizumab + chemo vs trastuzumab + chemo in 1L HER2+ advanced Gastric/GEJ - Zani + chemo: mOS 22.9 vs 19.6 mo (HR 0.76; p=0.0088) - Zani + TIS + chemo: mOS 27.0 vs 19.6 mo (HR 0.65); ~40% alive at 3 yrs - SoC for HER2+ in 1L 6/8
1
4
4
1,010
Sadly I’m not surprised. Journals quietly signing off on inflated framing has been all too common for years. Calling a descriptive OS a “positive OS result” is a textbook case, and I agree it should have been caught.
“Prespecified descriptive OS analysis.” Those words should give us pause. Calling this a “positive OS result” in a phase 3 trial manuscript is misleading when OS was outside the formal testing strategy. The results are encouraging, but an OS benefit has not been formally demonstrated in this analysis. I’m surprised this framing passed journal review. Oncologists and patients shouldn’t need to close-read a manuscript like English professors to understand whether a trial formally demonstrated an OS benefit. Put the bottom line up front. @Timothee_MD @oncology_bg @SusanGKomen @BCRFcure @OncoAlert @Annals_Oncology @myESMO @ASCO @AACR @SABCSSanAntonio
7
317
Thanks for sharing. Agree. The OS p is nominal, and it's open-label with 7.9% of controls withdrawing consent at randomization vs 3.3% on ribo. A 2.1-point gap when most relapsed controls didn't get a 1L CDK4/6i isn't a reason to change US practice imo.
NATALEE 6-y results are out! #ESMO26 2.1 delta in survival at 6 years. Thanks @Annals_Oncology for reporting subsequent therapy data! 👉Only 44.4% of control arm patients with distant recurrence received a first-line CDK4/6i Does this survival difference truly inform clinical practice in settings where CDK4/6i are standard of care for metastatic disease? In my opinion, the answer is no.
1
2
4
575
Agree access at recurrence is a problem. But if US patients get the CDK4/6i at relapse and OS barely moves, then persistent iDFS here mostly means delaying the same outcome, not changing it.
NATALEE study @myESMO shows persistent iDFS and emerging OS signal. Given treatment options for MBC, the treatment upon recurrence matters. Fewer than half the patients in the ET-alone arm get CDK46i on recurrence. Which poses the question: how relevant are OS data to US/OECD outcomes? In the online publication, the OS difference is smaller, and not statistically significant, in US/Western Europe. annalsofoncology.org/article…
1
99
Sobering, agreed. It missed its own pCR bar, though with no chemo comparator and pCR a weak surrogate in HR+ disease, that's all it can tell us. Three cases of grade 2 ILD and a death are a lot to see in patients treated with curative intent. The 2022 interim data already suggested anastrozole added nothing. In HER2-low disease, T-DXd's proven benefit is still metastatic.
Probably first negative trial for Trastuzumab deruxtecan. Talent trial. For early stage HR positive Her2 low EBC @myESMO #esmo26 @OncoAlert
1
3
292
Agree, and that monopoly is already eroding. Editors still decide what gets printed. They no longer get the last word on what it means.
I have said it for years: editors are the single weakest link in the academic system IMO This is a power that should not reside in central planners (see Hayek) but in the wisdom of the community * Disclosure: I am currently and have been an editor
1
1
6
1,252