Ankur Mehta

@AbiSivaMD @PathologyPat @muschollings Might help select I/o sensitive disease in this otherwise cold histology. Especially seeing mPIK3Ca enriched! Tissue based TMB still ideal. Nice correlative study!

Happy to be part of this publication highlighting the clinical and genomic characteristics of ultra-high tumor mutational burden (UHTMB) in metastatic breast cancer and the potential benefit of immunotherapy in this subset. @muschollings #bcsm

CAPItello-291試験で、PTENの免疫染色でPTEN lossの評価をみた報告。 NGSとの一致率は8割程度で、NGSでlossがなく、IHCでPTEN lossの判定でもCapivaの上乗せありそう。 これは納得かついいデータ。

@drsarahsam Congratulations! you will be missed at the Farber!

Today is my last day at Dana-Farber Cancer Institute. 💙🎗️ DFCI is a place unlike any other. The standard of care, culture of intellectual curiosity, the relentless focus on patients. A special thank you to Dr. Sara Tolaney and Dr. Nancy Lin for your gracious mentorship. There is no better place. Our hearts are full. We’re heading home to family. 💙 Soon I’m joining the @UMGCCC University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center as Co-Leader of Breast Oncology, with a deep commitment to growing the breast program for the people of Baltimore and the DMV. We plan to initiate a new multidisciplinary CNS Metastases Clinic, home to Maryland’s only Proton Center. 🧠⚡ @UMGCCC is one of 56 NCI-designated comprehensive cancer centers in the country, moving into a brand new state-of-the-art building, and on the rise under the visionary leadership of Dr. Taofeek Owonikoko. To every patient who trusted me: thank you and you are in the best hands. 🎗️ #BreastCancer #Baltimore #BrainMetastases #ProtonTherapy #Oncology #NewChapter #UMGCCC

Now out in @JCO_ASCO: The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease pubmed.ncbi.nlm.nih.gov/41805422/ @hthrparsons @FNavarroBioInfo @smelrefai @jesusanampa @jsparano @mfrimawi @RitaNandaMD @AngieDemichele @guptalabunc @FilipaLynce @ErinCobain @DrShelleyHwang @awolff @benhopark #ctDNA #BreastCancer #MRD

In met Prostate Ca, darolutamide is FDA-approved for M0 (non-metastatic) CRPC with the goal of preventing clinical progression — i.e., bone mets. These are pts with only biochemical progression (M0 disease) who have an approved drug whose endpoint is radiographic PFS. Is a similar rPFS benefit meaningful in breast Ca ?

Potential breakthrough for metastatic pancreatic cancer - DARAXONRASIB (Revolution Medicines): Ph3 RASolute‑302 in previously treated PDAC showed median OS 13.2 vs 6.7 months with chemo (HR 0.40, p<0.0001); met all PFS/OS endpoints and was well tolerated. Oral RAS(ON) inhibitor targets active mutant KRAS (mutated in ~90% PDAC) , driving tumor initiation, growth, metastasis and therapy resistance by hyperactivating MAPK/PI3K signaling. Targeting oncogenic RAS could finally turn a central tumor driver into a therapeutic vulnerability @DanaFarber_Hale @ASCO @PanCanResearch

Thanks Sarah, very helpful & imp to include these in guidelines for therapy change. Esp critical in bone only Mets & assessing ADC or I/o responses. Integrating radiology +tumor markers+clinical+ctDNA with rising TF helps(when scans equivocal)

Thnx for pointing out Mark! This should include trial mandated frequency of scans and testing, ex: on Herceptin, echo monitoring q3 mths in the absence of symptoms, makes no sense, especially if LVEF impact is reversible in all! We all have pts getting these ‘surveillance’ echocardiograms for years!

@dr_yakupergun @PTarantinoMD Agree with Paulo, it’s the best PFS of 44 mth in her2 positive disease so far! Destiny 09 was 40.7 mth in front line. Palbo is so well tolerated & low likelihood of neutropenia leading to infections, again manageable with dose mods if needed.

@PTarantinoMD 💯👍

I’m all for being critical in interpreting trial results. In this case, though, the PATINA results speak by themselves. The addition of a well-tolerated drug (palbo) improved PFS from 29 to 44 months, with a slight increase in mostly hematologic toxicities (usually asymptomatic). This means 44 months without progression from a deathly metastatic disease, 44 months without the need for chemo, 44 months with a favorable QoL. And hopefully we will eventually see improved OS (requires a long time to read out). It’s hard not to consider this beneficial for our patients.

PATINA@nejm. Since 2015 approval of palbociclib, we now finally confirm benefit in HR+Her2 pos mBC after a decade of use in HR+Her2neg mBC! unprecedented 44.3 mths PFS now possible in ~10% of all mBC Real world implications of PATINA, HER2C05 & DB09: 🔆 post induction THP -> HP + palbo /AI now SOC. 🔆 Her2C05 likely SOC in HRneg. But in select pts as tolerability - GI tox concerns if frail, low volume disease, where HP alone is easier. 🔆 Even in “exceptional” responders to THP, we should add Palbo early as better systemic control likely improves CNS PFS as already a signal in this subgroup. Significant absolute diff in CNS PFS of 6% at ~36 mths( ~13% vs 19%). 🔆 Brain Mets- if asymptomatic brain Mets at baseline ( ~12% in HER2CLIMB05, vs ~4% in PATINA) even in HR+, prefer Tucatinib as well established CNS efficacy even though it’s a shorter follow up of ~23 mths 🔆 Next ? Can we combine Tucatinib/Palbo/AI/HP for maintenance esp in Brain Mets? Barring payer coverage issues, there is at least some safety data in Ph 1b/2 trial that Palbo/Tucatinib combo is tolerable, although Palbo dose needed reduction to 75 mg for neutropenia. 🔆 TDxd induction might be ideal in brain Mets, followed by Tucatinib/HP/AI +/-Palbo in maintenance in HR+@NEJM @SABCSSanAntonio @DFCI_BreastOnc @breastcancer

The largest randomized trial of medical A.I. —Over 100,000 women in Sweden —radiologist + AI vs 2 radiologists, in follow-up —AI added led to 29% more cancer detected, 44% reduced workload, and —Less cancer dx in subsequent 2 years, and, when found, less aggressive thelancet.com/journals/lance…

PATINA is now out in @nejm. Among pts with HR+/HER2+ MBC progression-free after chemo induction, adding palbociclib to 1L ET+HER2-blockade maintenance prolonged PFS from 29 mo to an astonishing 44 months (HR 0.75, p=0.02). Congrats @Otto_DFCI & coauthors! nejm.org/doi/full/10.10…

Congrats @DrIacovelli + all Italian🇮🇹 team in executing a near impossible trial and paving the way —@NatureMedicine #TACITO @Unicatt @gianluca1aniro

Intrinsic subtyping in HR + Her2 neg, especially Luminal B which may be more endocrine resistant might help clarify risk. We need better agents for Lum B & not sure if adjuvant cdk4/6 alone is sufficient

• Early TNBC: 74.3% •Non–high-risk HR+/HER2−: 91.2% ⚠️~60% of monarchE-eligible patients did not receive adjuvant abemaciclib Underuse most evident in N1 disease and older patients 📌 N1 ≠ Low risk N1 + Grade 3 or tumor ≥5 cm = true high-risk biology ET alone is insufficient

Micrometastatic axillary disease after neoadjuvant treatment - The Lancet Oncology thelancet.com/journals/lanon… Post NACT, ypN1mi. Study asks if ALND reduces axillary recurrence at 3 yrs. Current SOC- SLND, targeted axillary dissection (TAD) + Regional Nodal Irradiation (RNI) if ypN1mic Key takeaways ✅ 3 y Axillary Recurrence (Primary endpoint) 2.0% (low) ✅ 1.7% with ALND vs 2.3% w/o ALND (P=0.92) ✅ overall safe to omit completion ALND in most, NOT ALL! ❌ in TNBC. 8.7% risk of recurrence at 3 yr (without ALND) vs 2.4% (with ALND), P=0.018. HR 3.83 ❌ omission of Nodal XRT in all HR 2.62. 🔆Practice affirming - in Non TNBC, safe to omit ALND but favor RNI. In TNBC clearly need RNI, and caution in omitting completion ALND. 🔆 Large sample size(1585 pts), multicenter, diverse groups of histology, stages included. 🔆limitations -retrospective ? possible bias if low risk pts selected for omission of ALND. Short f/u especially HR+ve pts with potential late recurrences. @breastcancer, @TheLancetOncol @ASCOPost @MontagnaGiacomo @SABCSSanAntonio

A must read! Key take aways 1) Stage III Her2+ still needs intensive regimens as underrepresented in THP trials 2) 6 vs 4 cyc of Taxanes ⬆️ pCR but tox⬆️ 3) agree with Paolo-combine genomic/ctDNA/radiographic response to adapt escalation in neoadj 4) wkly Nab-pac/Pac seems better alternative to Docetaxel

Which premenopausal, node -ve HR+, Her2 -ve pts can omit OFS vs Tam mono therapy. Per SOFT/TEXT trials absolute benefit was low ~3- 5 % in distant relapse free survival even in higher risk (G3,>T2,chemo treated) & only 2-3 % OS benefit! QOL is quite poor on chronic OFS -menopausal symptoms, bone loss, poor sexual health, arguably worse for some even compared to 4 cyc of adjuvant TC! Need trials to selectively de-escalate OFS.

Listening to #JenniferLigibel of ⁦@DanaFarber⁩ speak of the issue of #BurnOut in the medical oncology community here at our quarterly #NetworkProviderForum! I think she is amazing! Could listen to her all day! And it would reduce burnout too!!

Thanks for highlighting this issue. while it’s nice to have multiple drugs with same MOA- PARPi, BTKi,CDK4/6i, SERDs etc. resources are better spent on novel drug MOA to allow multiple lines & combinations that can allow CRs/ extend cumulative survival. It’s disheartening to see most money spent in each pharma promoting their version of the same drug with some nuance.