Francesco Schettini, MD, PhD 🇮🇹🇪🇸🇪🇺

A taxonomy of the factors contributing to the overtreatment of cancer patients at the end of life. What is the problem? Why does it happen? How can it be addressed?

Excellent work published in#ESMOOpen by #ChernyNI et al.👇🏻

doi.org/10.1016/j.es...

What a way to start 2025!!! I am extremely grateful to the commission that positively evaluated my application. But most of all, thanks thanks thanks to my mentor @prat-aleix-md.bsky.social for believing in me, sometimes even more than myself 😝

Oh, and happy new year from Sicily to you all

Now that it’s official, I can finally celebrate: I’ve been awarded a Juan Rodés contract starting in 2025, ranking 1st in 🇪🇸!

Ahora que es oficial, por fin puedo celebrarlo: me han concedido un contrato Juan Rodés a partir de 2025, ocupando el primer puesto en 🇪🇸!

RLY2608 is a mutant specific PIK3CA inhibitor sparing Wildtype Receptor.

2nd line PFS >11 months with fulvestrant.

Improved safety profile with low grade hyperglycemia, no rash, diarrhea, or oral sores.

Hoping this one moves forward!

#SABCS24 @oncoalert.bsky.social @oncbrothers.bsky.social

At #SABCS24 LBA session - @LoiblSibylle on the PADMA trial comparing 1st line ET + Palbo vs Standard Mono-CT in High Risk HER2-/HR+ metastatic BC and indication for CT

⬆️TTF and PFS w/palbo+ET

Reassuring data supporting 1st line CDK4/6i+ET as SoC

@oncoalert.bsky.social

For sure, outstanding discussion by prof Harold Burstein from @dfcibreastonc.bsky.social. Here some of his conclusions (and the previous algorithm was his slides as well as the comparison in toxicities and mPFS)

Maybe we can offer some hints at the poster spotlight session 2 tomorrow Dec 12 07:00-08:30 with our preliminary results of TARGET-POST-CDK study, PS2-07 😊
#IsabelGarciaFructuoso @prat-aleix-md.bsky.social @idibaps.bsky.social @hospitalclinic.bsky.social @oncoalert.bsky.social @ub.edu

Also, the toxicity profiles compared to other oral SERD was quite good. This positions the combo as the potential standard II-line for ALL patients progressing to CDK4/6i where the dependency on ER pathway is still there. BUT who are these pts? 👇🏻

BUT, differently from imlune alone, imlune+abema was also superior to imlune in ALL pts, including those without ESR1mut, and after previous I-line CDK4/6inhibitors (mostly palbo/ribo) and in PI3Kpathway-altered BC, with a mPFS that is superior to every ET-based regimen so far

My first takeaway from #SABCS24. The EMBER3 of new oral SERD imlunestrant vs fulvestrant or exemestane vs imlune+abemaciclib in HR+/HER2neg MBC. This study showed in II-line scenario that imlunestrant is superior to ET alone in ESR1mutant patients. AKA welcome to elacestrant 2 👇🏻

Barcelona!

Bluesy night before a very long trip to #SABCS24.

Una maravilla! Recomendadísimo

Use of the ESMO-Magnitude of Clinical Benefit Scale to guide HTA recommendations on coverage and reimbursement for cancer medicines: a retrospective analysis Several factors informed HTA outcomes for new cancer medicines. A high ESMO-MCBS score, defined as indicating substantial clinical benefit, increased the likelihood of a positive HTA outcome and short...

⭐️Use of the ESMO-Magnitude of Clinical Benefit Scale to guide HTA recommendations on coverage and reimbursement for cancer medicines: a retrospective analysis www.thelancet.com/journals/lan...

Big changes are coming…

One of the most important multi-cancer analyses on #ImmuneRelatedAdverseEvent grading and clinical outcome is out this week from @JNCI : https://buff.ly/499OIBj

The present and future of bispecific antibodies for cancer therapy - Nature Reviews Drug Discovery Bispecific antibodies (bsAbs) can mediate therapeutic effects beyond those of natural monospecific antibodies. This Review provides an overview of recent developments in the field of bsAbs for cancer ...

Review: The present and future of bispecific antibodies for cancer therapy

@ub.edu @idibaps.bsky.social @hospitalclinic.bsky.social

Finally, a huge thank you to #ESMO and #EvandroDeAzambuja, as without the #Fellowship programme I would have never had the possibility to do this research and probably be where I am now.

I would like to thank all the people involved in this study, but special thanks go to @prat-aleix-md.bsky.social who guided me through and pushed me to move forward, #FaraBrasó for her teachings and suggestions, @tomaspascualmd.bsky.social for giving me THAT database to "play with" in 2019 🙏🏻

More cool stuff can be found in the full publication available in OA at this link 👇 authors.elsevier.com/sd/article/S..., including cell lines experiments and further insights.

It's been several years of my life spent on this project and likely many more to come, following up on this.

In addition, we found out that molecular downstaging or persistence of ROR-P-low or Luminal A subtype from baseline to surgery showed a trend for improved outcomes

We then observed that both NACT and NET promote a molecular downstaging inducing molecular subtype shifting to luminal A or normal-like and to ROR-P-low-risk class

We took into account 3 different response type, i.e. molecular responders (i.e. ROR-low and Ki67 10% after treatment) and pathologic responders. Using multiclass SAM, we revealed differential baseline gene expression differences among responders and non responders to NACT and NET

When checking for clinicopathological and molecular factors predicting pathologic response, we found that PAM50 non-luminal subtypes at baseline were the only independent predictors of response to NACT, while for NET MMP11 mRNA levels were independently associated with RCB-II/III

First, we compared NACT to NET in a clinical practice cohort of 186 patients, and confirmed that NACT is associated with higher rates of RCB-0/I than NET in stage I-IIIB HR+/HER2- BC. Both in the entire study cohort, then after propensity score matching to mitigate selection bias

Finally out in @ESMO_Open the main findings of my #ESMO #Fellowship research project focused on the
identification of predictors of response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in HR+/HER2- #breastcancer.
What did we find? A thread 🧵

Only 3 weeks to #SABCS24, a meeting that promises to significantly impact the way we treat breast cancer. It will feature phase 3 data with novel SERDs, novel ADCs, immunotherapy, ctDNA monitoring, important biomarker analyses & so much more. Here’s my top 10 abstracts list— see you in San Antonio!