Raymond DeMatteo, PharmD, BCOP

Clinical Pharmacy Specialist in Early Drug Development at MSKCC | Former Lymphoma Pharmacist | Former Lab Rat

[Dr Amol Akhade @SuyogCancer]

Nice Infographics to Show
1-mechanism of resistance of ADCs used in Breast Cancer
2-structural details of Newer ADC being studied in Breast cancer
3- Timeline for approval of All ADCs by USA FDA in Breast cancer till date.

Useful for quick reference .

[Dr Amol Akhade @SuyogCancer]

What if this was a drug ?🙂

🆕 NEJM | June 2025
🎯 CHALLENGE Trial: Structured exercise after adjuvant chemo in colon cancer
📦 RCT | n=889 | Median FU: 7.9 yrs
🟠 3-yr structured aerobic program vs health ed alone
📈 Primary Endpoint: Disease-Free Survival (DFS)
🔹 HR 0.72 (95% CI: 0.55–0.94), p=0.02
🔹 5-yr DFS: 80.3% vs 73.9% (+6.4%)
🟨 Overall Survival (OS)
🔸 HR 0.63 (95% CI: 0.43–0.94)
🔸 8-yr OS: 90.3% vs 83.2% (+7.1%)
🧠 Other highlights:
🔻 ↓ Liver recurrence: 3.6% vs 6.5%
🔻 ↓ New primary cancers: 5.2% vs 9.7%
🔻 Improved cardiorespiratory fitness, QoL, 6-min walk
⚠️ AEs: ↑ MSK issues (18.5% vs 11.5%), mostly mild
No major safety concerns
🤔 What if this was a drug?
📢 “Breakthrough”
💰 $120K/year
📄 Fast-track approval
Instead, it’s just structured EXERCISE.
💡 Prescribe it like we would any other adjuvant therapy.
Congratulations to Authors and Dr Chris Booth 👏
#CHALLENGEtrial #ASCO25 @csoncol @oncology_bg @ASCO #ASCO25 @OncoAlert

[Aakash Desai, MD, MPH, FASCO @ADesaiMD]

🚨 FDA #accelerated approval: Telisotuzumab vedotin💉for advanced non-sq #NSCLC w/ high c-Met overexpression (≥50% 3+ IHC), 1.9 mg/kg q2 weeks
🧬 ORR: 35%
⏱️ DOR: 7.2 months
🔬 Companion Dx: VENTANA MET SP44
Another ADC joins #lcsm toolkit!
@LungCancerRx @OncBrothers @US_FDA

[Oncogene Cancer Research @OncogeneCancer]

Big breakthrough @AACR presented by @KCArbourMD: Oral drug zoldonrasib shows real promise for KRAS G12D #lungcancer, a group with no targeted options until now.

Compared to traditional chemo, this could be a game-changer. Hope is growing.
#AACR25 #lcsm https://t.co/4kSBdnkuGG

[Yakup Ergün @dr_yakupergun]

The Most Commonly Used Statistical Tests in Medicine: When to Use Which Test?

#Statistics

[John Pavlovitz Official @johnpavlovitz]

Kamala Harris didn't lose, America did.

As a nation, we collectively failed her—and in doing so we failed girls and women, the LGBTQ community, people of color, Muslims, Jewish people, immigrants, the sick, the poor, the elderly, the people of Ukraine, and Gaza, and the planet.

It's unthinkable, that instead of being able to celebrate a beautiful, hopeful new chapter in the story of this nation with a leader who appealed to the best of our natures—we will instead be holding a postmortem for democracy as we enter our 250th year, stewarded by a malevolent sociopath who despises empathy and shuns the law.

I truly thought we were better than this, that our shared humanity would show up. I thought we would reject this hatred and ugliness once and for all.

I hate being wrong about the majority of the people of this nation.

I don't know what's ahead. All I know is that good-hearted human beings are more necessary now than ever.

We did all that we could to avoid this moment, but now that it's here we'll just have to decide who we will be.

There is no way to comprehend or measure how grievous an error this is, but the only thing the decent people of this nation can do is wake up tomorrow and fight like hell for what we still believe is worth the fight, and we will.

I'll be doing that with whoever has the strength to join me.

I'm mourning the country we could have been and the one we apparently are—but I refuse to give up believing that compassion is the right path, that diversity makes us better, and that love is greater than fear.

[Lauren Averett Byers, MD @LaurenByersMD]

POP QUIZ: Is this a waterfall plot for a new lung cancer TKI? Nope…SEZ6 ADC for Relapsed Small Cell Lung Cancer (and other NECs). #SCLC #LCSM. @MDAndersonNews Thank you to the study team and all of our investigators, patients and families. @ASCO #ASCO24

[Oncology Brothers @OncBrothers]

#TDxD now @US_FDA approved for pan-tumor w/ HER2 IHC3+ solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.

Based on DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02:

- Dose 5.4 mg/kg
- Common AE: fatigue, ⬇️counts, nausea. ILD can be fatal.

#OncTwitter #MedTwitter #bcsm #lcsm #gism #gusm

[Jonathan Rosenberg MD @DrRosenbergMSK]

Very happy to see this in print! Congratulations to all involved in this transformative effort, and to the patients who may benefit from this combination therapy.

[Oncology Brothers @OncBrothers]

#ESMO23 Day 4 Highlights #CommunityOnc:

1. #CAIRO5 - mColorectal Ca

2. #TROPIONBreast01 - HR+ #BreastCancer

3. #PSMAfore - mCRPC #ProstateCancer

#LungCancer
4. #TROPIONLung01

5. #MARIPOSA

6. #MARIPOSA2

#gism #lcsm #bcsm #crcsm #OncTwitter @myESMO #Medtwitter

1/7

[Raffaele Colombo @raffcolo]

At #ESMO23 navigating all the new #ADC data?

Must read papers:

ADC dogma: https://t.co/qqKv0JgD4b

ADC toxicity: https://t.co/1z7sg41cpp

ADC clinical development: https://t.co/xgmVjfBQmv

ADC targets: https://t.co/EaECF4APGb

ADC payload exposure: https://t.co/GgnQlWMkdH

[Jonathan Rosenberg MD @DrRosenbergMSK]

EV-302 data changes the game in metastatic UC. Congrats to @tompowles1 for a well conducted study and great presentation, and to the entire EV-302 study team @IyerGopa. Congrats to @apolo_andrea for her insightful discussion. @MSKCancerCenter @MichvdHeijden @BladderCancerUS

[Enrique Grande @drenriquegrande]

🎯EV 302 summary:

📌PFS 12.5 mo vs 6.3 mo HR 0.45
📌OS 31.5 mo vs 16.1 mo HR 0.47
📌ORR was 67.7% and 44.4%
Everything favored Enfortumab vedotin + Pembro arm

https://t.co/5dYJ6NZpnX

I can’t wait to see the data, particularly subgroup analysis by elegibilty to cisplatin and safety.

However, few doubts that guidelines will need to be updated soon

Thanks to the patients and clinical trial team led by @tompowles1

See you on Monday
@OncoAlert @Uromigos @montypal @DrChoueiri @apolo_andrea @ERPlimackMD @MattGalsky @sonpavde @PGrivasMDPhD

[Eddie Cliff @Eddie_Cliff]

The #sotorasib @FDAOncology ODAC is interesting so far -

CodeBreaK 200 is a good reminder that Hazard Ratios are hard to interpret clinically.

Although interval censoring analysis still shows a statistically significant HR, it is hard to find 5 days' PFS difference convincing

[Stephen V Liu, MD @StephenVLiu]

Report @JTOonline that some targeted agents (TKIs) inhibit MATE-1 and falsely elevate creatinine. Cystatin C levels may be a better measure of renal function. Seen with certain #ALK #RET #MET #ROS1 #NTRK inhibitors. #LCSM

https://t.co/KtBTZqZmmQ

[Brendan Guercio @BrendanGuercio]

(2) Enormous gratitude for mentorship of @IyerGopa @DrRosenbergMSK @MFBerger1 @DSolit & others who made this work possible. From a cohort of >1500 urothelial carcinoma tumors, we identified >400 FGFR2/3 altered cases. FGFR3 was common, but FGFR2 alterations were exceedingly rare

[Vivek Subbiah, MD @VivekSubbiah]

📣Super thrilled to share our paper on RLY-4008, the First Highly Selective FGFR2 Inhibitor with Activity across FGFR2 Alterations & Resistance Mutations, published in @CD_AACR !
👉🏼Huge thanks to team at Cancer Discovery & @AACR for making the front page & the entire paper so visually appealing  👏🏼#PrecisionMedicine 🧬🎯#cancerresearch @OncoAlert @ElizSMcKenna @Relay_Tx
@TaliLev123
👉🏼Free Link: https://t.co/DmMttMep3o

[Dra. María Natalia Gandur Quiroga @nataliagandur]

✅ 🔝🔝Understanding the mechanisms of #resistance to #immunecheckpoint. recommended reading
@OncoAlert @OncoReporte #OncoAlertAF @BritishJournal
✴📢 New Mechanisms of T-Cell Desertification and Exclusion: Lessons from Metastatic Uveal Melanoma 🧪🔬

🔍 Key Results, Messages, and Conclusions:
1️⃣ Differential Response to Immunotherapy:
🟣mUM is universally refractory to ICT despite similarities with cutaneous melanoma.
🟣Nivolumab shows favorable outcomes in skin melanoma but not in mUM.
🟣mUM provides insights into ICT resistance in cold tumors.

2️⃣ #BRCA1-Associated Protein 1 (BAP1) Loss and Immune Suppression:
🟣#BAP1 deficiency impacts UM's immune landscape and prognosis.
🟣Upregulated immune suppressive genes accompany BAP1 loss in UM.
🟣Mechanisms of local immune suppression influence UM's immunogenicity.

3️⃣ #βCatenin Upregulation and T-Cell Exclusion:
🟣β-Catenin contributes to immune exclusion and ICT resistance in mUM.
🟣Fibrosis-mediated T-cell exclusion traps TAMs and TILs in fibrotic areas.
🟣Targeting β-catenin, IDO1, #PDL1, and TAMs may overcome ICT resistance.

4️⃣ Adipophilin Loss and Metabolic Shift:
🟣Loss of adipophilin expression correlates with poorer survival in UM.
🟣TME's metabolic shift impacts immune responses in mUM.
🟣Small molecules and inhibitors offer potential therapeutic applications.

5️⃣ Novel Therapeutic Approaches:
🟣Tebentafusp shows promise in recapitulating hot tumor features in mUM.
🟣Darovasertib and selumetinib disrupt UM cell growth and immune responses.
🟣Personalized cell therapy with neo-TCR transgenic cells overcomes T-cell desertification.

6️⃣ Rational Combinations and Future Directions:
🟣 Enhancing DC vaccination combined with ICT improves anti-tumor responses.
🟣Blocking MIF/CD74 signaling, inhibiting Clever-1, and targeting immunosuppressive elements enhance immunotherapy responses.
🟣 Combinatorial approaches involving VEGF-targeting therapies, IL-10/STAT3 inhibition, TBK1 inhibition, and targeting MICA/MICB stress proteins show potential.
🟣Ongoing research and clinical trials will optimize these approaches for mUM management.

🔎 Conclusion:
Understanding T-cell desertification and exclusion in mUM is essential for effective immunotherapy. Personalized cell therapy, targeted therapies, and rational combinations offer hope for improved outcomes. Further research and trials are needed to validate and optimize these approaches for managing mUM. #Immunotherapy #Melanoma #Research #PrecisionMedicine https://t.co/vTfG5urs83

[Dra. María Natalia Gandur Quiroga @nataliagandur]

📢 🔝🔝🔝 Advances GU TUMORS

🌟Renal Cell Cancer
1️⃣ Triplet therapy in RCC: The COSMIC313: The study showed improved progression-free survival (PFS) with a hazard ratio (HR) of 0.73 and overall response rates (RR) of 43% versus 36%.
2️⃣ Subset analysis of the trial suggested the benefit of triplet therapy was seen in the intermediate-risk population.
3️⃣ The higher toxicity burden of the triplet therapy must be considered, and overall survival (OS) data is yet to be published.
4️⃣ Other ongoing triplet trials, such as MK-6482-012 and MK-1308A, are further investigating the combination of pembrolizumab with belzutifan and lenvatinib, respectively, to clarify the issue.
5️⃣ Updated analysis on PD-1-based combinations in front-line disease showed no major shifts in response rates or PFS, and the overall survival signals for PD-1 combinations appeared less compelling than initially thought, particularly in good-risk disease.

🌟 Bladder Cancer
1️⃣ Antibody drug conjugates (ADCs) in bladder cancer: #Enfortumab vedotin (EV), an ADC targeting nectin-4, showed a 30% reduction in the risk of death compared to chemotherapy in heavily pretreated urothelial cancer.
2️⃣ Sacituzumab govitecan (SG), a Trop-2 targeted ADC, showed a response rate of 27% in platinum-refractory disease as a single agent and a response rate of 41% when combined with pembrolizumab.
3️⃣ Trials combining chemotherapy with ICIs have generally shown no benefit, except for maintenance ICI following chemotherapy. The reasons for the additive effect of EV/pembrolizumab combination are unclear, but the targeted nature of ADCs might explain it.

🌟Prostate Cancer
1️⃣ Triplet therapy in prostate cancer: Showed rPFS and OS compared to ADT and docetaxel alone in mCSPC.
2️⃣ ICIs: #pembrolizumab mCRPC no OS benefit. Biomarkers are needed
3️⃣ Lutetium-177 (177Lu)–PSMA-617, demonstrated an OS benefit in mCRPC. However, its superiority over other standard therapies, such as cabazitaxel, has not been investigated.
4️⃣ Nonmetastatic high-risk prostate cancer: ABI + AAP + ADT improved metastasis-free survival and overall survival in high-risk prostate cancer. The addition of enzalutamide +AAP + ADT did NOT provide additional benefit.
@tompowles1 @ChrisSweens1
@OncoAlert @SauUrologia @CAU_URO @InstitutoRoffo @OncoAlert https://t.co/e7IOFINMsh

[Tom Powles @tompowles1]

I think the most important issue is giving cisplatin based neoadjuvant chemotherapy, rather than focusing on the specific regimen. I don’t think that has to be DDMVAC x6 based on VESPER (excellent investigator study). Gem/Cis remains reasonable.