Paolo Tarantino
@PTarantinoMD
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MD, PhD, Medical Oncologist | Clinical Fellow @DanaFarber | @Harvard. SoMe Editor @ESMO_Open. Interested in breast oncology, HER2, ADCs and good music.
Boston, MA
Joined January 2018
In 2020 we proposed to add a #HER2Low slice to the HER2 pie chart, an addition that has now entered practice. But further changes await us in the coming years. Excited to share our latest Cancer Discovery piece, outlining the present & future of HER2-low!.
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Standing ovation after the #ASCO22 Plenary presentation of DESTINY-Breast04 by Dr. Shanu Modi. A beautiful, powerful moment, that will remain in the history of breast oncology.
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Reading good review articles can shape ideas, help connecting the dots and understanding what’s coming ahead in science. Here’s 10 review articles that helped me shape my views on breast oncology and drug development:.
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Historical moment for GU oncology. @tompowles1 brilliantly presents the results of the EV-302 phase 3 trial, showing a doubling of OS for patients with mUC receiving 1L enfortumab vedotin+pembro vs SoC platinum-based chemo. ADCs keep shining and improving outcomes! #ESMO23
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The MRD revolution has started. In this trial (n=455), stage II CRC pts were randomized to standard management or ctDNA-guided (no adj chemo if ctDNA negative). ctDNA guidance halved the use of chemotherapy, preserving outcomes. We need the same in #bcsm!.
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In ten days, the presentation of DB-04 may redefine the way we classify and treat breast cancer. Here’s ten HER2-low facts you need to know before attending the ASCO Plenary Session:.
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T-DXd has shown remarkable activity for treating HER2-positive and HER2-low breast cancers. However, it may soon expand its reach, and become a treatment option even for HER2-0 tumors. Here’s the 10 reasons why:.
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Two weeks to #ESMO22. Plenty of important breast cancer studies to be presented at the Congress, some that will immediately inform practice. Here’s 10 key abstracts to keep an eye on. See you in Paris! 🇫🇷
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Fascinating article just out on @Nature, showing that a trispecific antibody targeting HER2, CD3 & CD28 was able to induce T-cell dependent tumor regression in HER2+ and HER2-low breast tumors. The era of cancer immunotherapy has only just started.
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Happy Thanksgiving with the most impressive KM curve you’ll see today. PFS for first line nivo/ipi vs chemo in MSI-H mCRC. 🛻 Truck test: <0.001.
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10 days to #SABCS23, 10 abstracts to keep an eye on. They include practice changing studies, highly awaited updates, important biomarker analyses, & RWD, among others. Not an easy selection: many more impactful studies will be presented. Full program here:
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Ten days to #ESMOBreast22, ten abstracts to keep an eye on. Important new clinical and translational data for every subtype of breast cancer: make sure not to miss it!.#bcsm
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Honored to have our pivotal JCO paper on HER2-low breast cancer cited in the Plenary presentation and discussion of the DESTINY-Breast04 trial. Huge emotion to see what we had envisioned in 2020 becoming reality, changing practice. Read it here:
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What is HER2 « ultralow » breast cancer, and why should you care?. A thread:.
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What genomic alterations drive HER2-low breast cancer? Do they differ in HER2-0 tumors? We analyzed data from >1000 patients receiving NGS at @DanaFarber to answer these questions. Incredibly proud to share the results, now published on @NatureComms. 🧵
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🔥 HUGE news in breast oncology. The #NATALEE phase 3 trial of adjuvant ribociclib for stage II-III breast cancer met the primary endpoint of iDFS!.
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☕️ Since I’ve been seeing a lot of debate in the field lately, I’ve decided to provide a set of Guidelines for the management of a good 🇮🇹 coffee. 1️⃣st - get a Moka. Better if an old one: just as wine, it gets better with the passing of time. Wash the Moka. Open the Moka. [1/5]
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Excited to share our #JCO work on HER2-Low BC, an emerging entity with potentially relevant clinical & translational implications. @curijoey @FAndreMD @ErikaHamilton9 @stolaney1 @penaultllorca @darioT_ @antoniomarraMD @OncoAlert @LaStatale @ASCO_pubs. 1/6
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HER2: a remarkable story of precision oncology. Check this wonderful Nature review on targeting HER2 beyond breast. 👉Important to remember: now that we have an agnostic anti-HER2 drug approved (T-DXd), every adv cancer patient should get HER2 testing!.
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T-DXd is approved for the treatment of patients with ANY treatment-refractory HER2+ (IHC 3+) tumor, making of it the first agnostic ADC. Unlikely to be the last. Key priority: ensuring that HER2 testing is expanded across cancer types. Exciting times!
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In Napoli, when something good happens to you and you’re happy, you get an espresso, but instead of one you pay two. The second is called “caffè sospeso”. Someone in need, later that day, will come and ask “is there any Sospeso?”. It is a way to offer a coffee to humanity.
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Expectations for #ESMOBreast22 were high, but they were ultimately widely exceeded! Great in-person and virtual attendance, important new data & brilliant educationals made of this congress a terrific experience. Here’s my #top10 (+ bonus) Take Home Messages from #ESMOBreast22
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The most controversial meta-analysis of the year is now published on @TheLancet. Anthracyclines improved outcomes when added to adjuvant taxanes, but only when administered concurrently. No apparent benefit for sequential schedules, which are current SoC.
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ADCs are among the most rapidly expanding treatment modalities in oncology, with 11 ADCs approved and >200 in active development. Here’s 10 facts to know to prepare for the rise of ADCs🧵.
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So proud to see the diffusion of our review on ADC toxicities, with already 25k accesses and >300 Altmetric! The article will be made free to access and download in the days surrounding #AACR24, starting today: download a copy if you have interest in ADCs!
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2023 opens with my first article as senior author: a practical recap of how we can treat #HER2low breast cancer based on currently available data, led by the awesome @IlanaSchlam! Read it here: #bcsm @stolaney1
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DIANA-5: randomized trial of an active Mediterranean dietary intervention (vs control) to reduce breast cancer recurrence. 1542 pts randomized. No RFS benefit (HR 0.99). No evidence to recommend any specific “anti-cancer” diet to pts with breast cancer.
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What a decade, for breast oncology
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For those asking about the location: meet #Atrani! With its 798 inhabitants, Atrani is the smallest town of the Amalfi Coast, & yet one of its most charming corners. Much less known than Positano or Amalfi, it still retains a unique authenticity, together with an astonishing sea!
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1960s. My grandparents’ grocery shop in Torre del Greco 🇮🇹. My dad used to study medicine in the back-shop, while eating fresh mozzarella with bread.
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How can we identify upfront which TNBC patients will present a brain relapse? 5 letters: ctDNA❗️. #ASCO21 Abstract 507 - among 323 TNBC patients, nearly all of those with detectable CSF-ctDNA developed brain mets, whereas only 1% in the ctDNA- group relapsed in the brain
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We have a new standard of care second line treatment for HER2+ metastatic breast cancer
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32 panelists from 9 countries, 20 statements, one year of intense work (ASCO22->ASCO23). I’m deeply honored to share the results of the first ever Consensus on HER2-low breast cancer, supported by ESMO and now published on @Annals_Oncology. Read it here:
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The DAISY trial of T-DXd in MBC with variable HER2 expression is out on @NatureMedicine. Many important findings, including a similar ORR with T-DXd in HER2-low (37.5%) & HER2-0 (29.7%) MBC. Congrats to @FerMosele @FAndreMD et al for this impressive work!
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The new #Halgorithm for treating HR+/HER2- metastatic breast cancer. @DrHBurstein @SABCSSanAntonio @DFCI_BreastOnc #bcsm #SABCS24
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@morellifit The place in the photo is Atrani, SA (Campania region), quite far from Sardinia.
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The results of SONIA are out on @Nature. 1L use of palbo did not improve PFS over 2L use, but led to more AEs & costs. An evolving treatment landscape challenges its interpretation— yet it shows that sequencing trials are possible. Congrats to the authors!
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Agnostic ADCs are finally here. Huge opportunity for thousands of patients, but plenty of challenges! We need better biomarkers, an improved understanding of ADC sequencing and strategies to decrease toxicities. @PestanaRC @curijoey @CCortiMD @stolaney1
New Review | Antibody-drug conjugates: Smart chemotherapy delivery across tumor histologies @PTarantinoMD & @curijoey et al provide a comprehensive recapitulation of current indications, future challenges & opportunities in this emerging field.
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After today’s announcement of elacestrant, I took a moment to look back. What I saw, was an EPIC year for the treatment of breast cancer. Breast oncology is moving SO fast, we’re getting better at treating this disease day by day. What a time to do research in oncology!
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In a large (≃1000) RW cohort from @DanaFarber, consistently with prior reports, we found that nearly 30% of breast tumors changed HER2 status after neoadjuvant treatment. This only impacted prognosis if HER2+➡️ HER2-neg. Our latest article now out on EJC.
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Unfortunately true: novel ADCs are much more potent & effective than 1st gen ones, yet the higher potency comes at the cost of more chemo-related toxicities. In our recent Nature Review we suggested some strategies to mitigate toxicity of novel ADC (🧵):.
@SKabrajiMD ADCs keep getting more toxic! What’s going on? Help, @PTarantinoMD!.
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pCR ≠ cure (unfortunately). In this important work, Huober et al. analyze data from >2000 BC patients with pCR after NACT, showing that positive nodes, cT3/4 & lobular histology predict worse prognosis (up to 15% risk of recurrence at 4 years) despite pCR.
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Does T-DXd work in HER2+ BC active brain metastases? Pretty clear answer in the below waterfall plot from #TUXEDO1 phase 2 trial, now published on @NatureMedicine. Impressive IC-ORR of 73%, mPFS 14 months, QoL maintained during Rx. Congrats to the authors!.
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New from #ASCO24: CROWN 5-yr update: In pts w/ advanced ALK-positive #NSCLC, median PFS was not reached w/ lorlatinib vs 9.1 months w/ crizotinib. 92% of pts assigned to lorlatinib were free from intracranial progression: #ASCODailyNews @bensolomon1 #lcsm
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ADCs enable an improved delivery of chemo, expanding its activity, but not necessarily decreasing its side effects. Why is that? How can we reduce the toxicities of ADCs? . Glad to share our @NatRevClinOncol article on how to optimize the safety of ADC! 🧵.
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Truly impressed by the interest generated by our review on optimizing the safety of ADCs, ranked 1st among articles of the same age on @NatRevClinOncol!. ✳️ You can now use this link to read the article without paywall 👉
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What a ride! Four intense days of presentations, discussions, insights & networking. @SABCSSanAntonio never disappoints. Here’s my 5 take-home messages from these days. As usual, these are not exhaustive, as #SABCS21 was truly full of amazing science and striking advancements.
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Updated results of pralsetinib in RET+ NSCLC. 100% (100%!) of treatment-naive patients experienced a disease shrinkage. The CT scan of the first patient we treated in the trial is still on my desk, reminder of the transformational power of good science.
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Correct! Anthracyclines were originally discovered in Italy approximately 70 years ago by a company named Farmitalia. A member of the team went on expedition to Castel del Monte, in Puglia, in which soil he identified a strain of Streptomyces producing a substance with
Where does the name of Adriamycin (aka Doxorubicin) come from?.
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The KM curve everyone’s been waiting for. Adjuvant ribociclib for 3 years significantly improved iDFS in patients with stage II-III HR+ BC, with 25% reduction in the risk of recurrence & a 3-year iDFS delta of 3.3%. #ASCO23
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The formatted version of the ESMO Consensus Statements on HER2-low breast cancer is finally published on @Annals_Oncology. We hope it will prove helpful to navigate the evolving landscape of HER2-low breast cancer & to prepare for further upcoming changes!.
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Important analysis from #KATHERINE now published on Breast NPJ. Do patients with HER2 switch (pos->neg) after NACT still benefit from adjuvant T-DM1? This happened in 8.3% (70/845) of KATHERINE patients, & those in the T-DM1 arm clearly had improved iDFS.
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Excited for the upcoming #ESMOBreast23, which will feature impactful new data and many outstanding educational sessions. Wonderful job by Congress Co-Chairs @ErikaHamilton9, S. Delaloge & SB Kim plus the whole Scientific Committee. Here’s my personal top 10 oral presentations!👇
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Is #HER2low a distinct BC subtype? Among >5000 pts from DFCI/Brigham, we found no relevant difference between HER2-low & HER2-0 BC. ER-exp determined disease behavior & was positively associated with HER2-low exp. Huge thanks to @stolaney1 & all coauthors!.
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Impressive report in @NEJM. In a cohort of pregnant women with unusual clinical cfDNA-sequencing results, 52/107 were found to have a cancer via whole-body MRI, with a sensitivity of 98.0% and specificity of 88.5%. Physical exam & labs were of limited use.
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Press release from DESTINY-PanTumor02: T-DXd met the prespecified target for ORR & demonstrated durable responses across 268 patients with multiple HER2-expressing advanced solid tumours. 🔥Are we close to the first histology agnostic approval of an ADC?.
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OS results of KN-522 out in @NEJM. Terrific news: adding pembro to neoadjuvant chemo for TNBC saves lives (5% 5-year Δ). Bad news: we’re stuck with giving 5 drugs to all patients with stage II-III TNBC, with permanent toxicity for many. Biomarkers, please!
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Less than 48h to #ESMOBreast24: time for the #top10 abstracts. Highly awaited readout from IMp132, safety update of important ph 3 trials (TB01, NATALEE), intriguing biomarker analyses from large datasets (HER2DX, monarchE) and much more. Promises to be a terrific congress! #bcsm
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“Less than 1% of the ADC reaches the tumor after its infusion”
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Does T-DXd work in patients with active HER2+ BC brain metastases that have progressed on prior tucatinib? In this case series of 5 heavily pretreated patients, T-DXd had an intracranial response rate of 100%, including in tumors insensitive to tucatinib.
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Incredibly excited to see our article on optimizing the safety of ADCs making it to the cover of the August issue of @NatRevClinOncol! Also, glad to announce that the article will be open access for the next month! Read it here:
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Can we distinguish aggressive metastatic tumors from more indolent ones with a blood draw? Just out on @Annals_Oncology an interesting analysis by @StoverLab & colleagues, which found a strong prognostic value for ctDNA-derived tumor fraction.
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Group of oncologists moving toward Conference Room A at @ASCO 22 - #AmalfiCoast Edition 🇮🇹 . #BackHome #PathOfGods
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Capivasertib is now approved in combo with fulvestrant for pts with pretreated ER+/HER2- MBC whose tumor has an alteration in PIK3CA, AKT1 or PTEN (approx 40%). More important than ever to perform NGS/ctDNA to select the best 2L treatment after CDK4/6i.
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Otto Metzger (@Otto_DFCI) presents the practice-changing results from the #PATINA phase 3 trial: adding palbociclib to maintenance ET after 1L THP for HR+/HER2+ MBC significantly and meaningfully improved PFS (44 vs 29 months, HR 0.74, p=0.007). 44 months!!!!!!!!!!!!!!!!!!!!!!!!
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Happy holidays!.Wish everyone peace, joy, and wonderful times with the loved ones!. And no worries about weight gain: according to @NEJM it’s <500g, and it only takes a little jogging in 2023 🏃🏻♂️.
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The OXEL trial, led by @FilipaLynce, is out on @NatureComms. Among 45 pts with residual TNBC after NAT, adjuvant nivo/cape were well tolerated, increased peripheral immune score & led to numerically improved 2y iDFS (91%) vs nivo (47%) or cape alone (53%).
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GeparNuevo of neoadj chemo+/-Durva for TNBC is now published on @Annals_Oncology. Similar to KN522, it showed a survival benefit with IO. Different from KN522, this was achieved with neoadjuvant-only IO, & seemed to confer similar benefit regardless of pCR.
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PARP inh, IO, Saci, T-DXd. In just few years, treatments for TNBC have moved significantly beyond traditional chemo. So much more, however, remains to be done. In this paper, Paola Zagami & @DrLisaCarey highlight key milestones & future directions in TNBC.
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Can we improve MBC pts outcomes by switching ET upon emergence of circulating ESR1-mut? In #PADA1 , now out on @TheLancetOncol, switching from AI/palbo to fulvestrant/palbo doubled PFS. Important proof of concept, that will be further explored in #SERENA6.
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Truck test: ✅
First results of the CM8HW are out! Nivo/ipi vs chemo in 1st line dMMR mCRC. We knew it would be positive, but wow 🤯 HR 0.21 for PFS and + across all subgroups. No crossing of the curves! Toxicity very manageable (don’t be scared of low dose ipi1).
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Sacituzumab Govitecan is now approved by the FDA for HR+/HER2- MBC pts after ET and ≥2 lines of chemo, based on the sign OS benefit seen in #TROPiCS02. Congrats to all the investigators! @stolaney1 @hoperugo @JavierCortesMD @dradityabardia @jhaveri_komal .
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The largest study to date (N=1.13M❗️) on the prognostic value of HER2-low expression is out on @JAMAOnc. With an HR 0.98 & overlapping OS curves, HER2-low confirms not to be a relevant predictor of prognosis. Congrats to the authors for this huge analysis!.
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T-DXd is now approved by the FDA for patients with HER2-low MBC pretreated with one chemo, or with rapid recurrence (<6 months) after adjuvant therapy. A historical approval, that will lead to improved survival for a large population of patients with MBC.
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It turns out that our review on 40 years of ADCs marks my 100th scientific publication. What a journey!. I took this opportunity to look back and try connecting the dots of my scientific career. Here’s 10 key articles that defined my research path over the past 5 years: 🧵.
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Important point on the MoA of ADCs by Pat LoRusso. Radiolabeled antibody studies showed <1% of tumor uptake with antibody therapies. @VriesElisabeth
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The longest follow up to date of a metastatic trastuzumab trial: after 20 years from receiving TCH, 10% of the patients included in this phase 2 study was still alive. How to recognize & increase the rate of long-term survivors? 👉
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