KRAS wild-type

#OpenAccess from @FoundationATCG Genomic landscape of clinically advanced KRAS wild-type #PancreaticCancer Approximately 8% of pancreatic cancers are KRAS wild type, and many harbor actionable alterations. https://t.co/OmpTdg0OYU (@Aiims1742)

BI-2493 / BI-2865: non-covalent inhibitors, binding the inactive state of KRAS, blocked the activation of wild-type KRAS and a broad range of KRAS mutants, including G12A/C/D/F/V/S, G13C/D, V14I, L19F, Q22K, D33E, Q61H, K117N and A146V/T. @Boehringer #LCSM https://t.co/7m549MX20c (@HHorinouchi)

While we wait for better quality pics.. 😉 @VerastemOncolog @BanerjeeSusana @ASCO #ASCO23 RAMP201 #LGSOC #ovariancancer Phenomenal efficacy, safety data ▪︎RAF-MEK clamp avutometinib/ FAKi Defactinib. •Confirmed ORR 45% •KRASm 60% •KRAS WT 29% •(Unconfirmed ORR 52%-73%-29%) https://t.co/X6u3De05v4 (@CrozrX)

Now at #ASCO23: Dr. @gandhi_shipra on DC vaccine/pembro to address unmet need for patients with asymptomatic brain-metastatic #TNBC or HER2+ #breastcancer, and Dr. Rachel Frascati sharing promising findings on CIMAvax/nivo for patients with wild-type KRAS #NSCLC #lungcancer (@RoswellPark)

#OpenAccess in @ESMO_Open Smaller panel, similar results: genomic profiling and molecularly informed therapy in #PancreaticCancer By @SivekeJ eat al https://t.co/oulUjClhIZ Reiterating the importance of chasing down KRAS wild type cases for alternative actionable drivers. (@Aiims1742)

🔥BRAF-Driven Pancreatic Cancer: Prevalence, Molecular Features &Therapeutic Opportunities @AACR https://t.co/lRnVm3qUQ9 👉enriched in KRAS WT (10% of cases) 👉V600E , N486-P490 deletions & fusions (2-4%) 👉💊🎯for BRAFi, MEKi & combinations.. case reports.. @myESMO @OncoAlert (@ArndtVogel)

Preprint using @carisls multi-omics profiling data by @DrJashDatta et al reports how young onset #PancreaticCancer is distinct at genomic & transcriptomic level from “usual” age of onset disease. https://t.co/kDtAFdmmEm Higher prevalence of KRAS WT disease & alternative drivers. (@Aiims1742)

#PostTest Q2️⃣ #TumorBoardTuesday 👉🏽 Free CME (AMA & MOC) 🔗https://t.co/CRWgzGDAf7 🔬Path results for 62yo 👨🏾‍🦳 with left-sided, metastatic #ColonCancer (unresectable liver mets) who has undergone 1 cycle of FOLFOX: disease is KRAS wild type 🧐What would you add to tx regimen? (@RischZack)

@EileenMOReilly dawn of #KRAS inh’s beyond #G12C, young onset #PDAC w/signal of KRAS WT, #KRAS WT #pancsm exquisitely targetable, & building on #POLO maintenance concept in #DDR #PancreaticCancer Now at @CSCancerCenter 4th Annual GI Tumor conf https://t.co/7s8rEqg0r4 @OncoAlert (@jgong15)

Absolutely critical not to miss KRAS wildtype #PancreaticCancer as this subgroup (of differing size) often has valuable targeted treatment options available to them. #pancsm 💜 (@BenWestphalen)

An important caveat here that also applies to #PancreaticCancer samples with wild type KRAS. Almost a third of cases did not demonstrate driver fusions on DNA NGS, but only on RNA based analysis. Important to chase these actionable fusions in wild type KRAS cases. (@Aiims1742)

Not that this is unexpected but just a reiteration that #PancreaticCancer is really the biggest enchilada when it comes to somatic KRAS alterations. The data also contains information on significant co-occurring & mutually exclusive mutations (latter highlighting KRAS WT drivers) (@Aiims1742)

Case report in @JCOPO_ASCO Clinical Response to a HER-3/ERBB3 targeted Monoclonal Antibody, in a Patient With Metastatic #PancreaticCancer Harboring an NRG1 Fusion. https://t.co/Y6VKGpRn08 Younger onset PDAC (this was in a 38y old) with WT KRAS 👉🏽 Chase those fusions! (@Aiims1742)

Exceptional Response to Erdafitinib in FGFR2-Mutated Metastatic #PancreaticCancer #OpenAccess in @JNCCN from @DrHendifar & colleagues @CedarsSinai https://t.co/pBdy0yqRC9 For young onset, KRAS wild type pancreatic cancers, don’t forget to look for alternative driver fusions. (@Aiims1742)

🔥Comprehensive characterization of KRAS WT #pancreaticcancer🔥 @NatureComms https://t.co/Z8m292E6Bg 👉high freq. of fusions (6-67%)>BRAF, NRG1, NTRK, FGFR2 👉R5A2, PROX1 & chr1q amplification > druggable 🎯? 👉transcriptome similar to #CCA 🧐KRAS testing in #PDAC key @myESMO (@ArndtVogel)

Adding another recent #KRAS WT #PDAC case w/#FGFR2 fusion w/exceptional response to #erdafitinib to the collection from our @CSCancerCare team @DrHendifar @DrArsenOsipov #pancsm @PrecOncNews https://t.co/9o8kNJFLmS @JNCCN @TumorBoardTues (@jgong15)

🔥FGFR2 fusion in metastatic pancreatic ductal adenocarcinoma: Is there hope? 🔥 https://t.co/Pjgui96OTQ ✅4 intersting cases responding to FGFRi 👉all KRAS WT with comparable long survival 🧐non-typical fusion partners 🎯Early NGS in KRAS WT #PDAC❗️ @myESMO @OncoAlert (@ArndtVogel)

KRAS wt #pancreaticcancer has a unique genomic profile and better outcomes. Watch for a higher rate of targetable gene 🧬 fusions in this subgroup. @Nature @sepideh_gholami @SyedAAhmad5 @pashtoonkasi (@HKennecke)

In metastatic colorectal cancer (KRASwt), 2nd-line cetuximab extends median OS ~4 months 1st-line cetuximab+chemotherapy extends median OS ~4 months (vs chemo) Suggests that cetuximab could still have a benefit to give at 2nd-line for HNSCC. [Fig 4I, https://t.co/4WJWHuddOo ] (@ac_palmer)

Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma | Nature Communications https://t.co/Xj4Ot866tX (@jonathanloree)

#openaccess #Researchpaper @Nature_NPJ #PrecisionOncology - on KRAS wild type #pancsm #patients ✅67% oncogenic fusions🤝 ‼️ similarities to cholangiocarcinoma @pashtoonkasi @graokane @KenOliveLab @ArndtVogel @UmutDisel @OncoAlert 🚨#PrecisionMedicine https://t.co/QTcogjBz4V (@BenWestphalen)

Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma | Nature Communications https://t.co/TJi8X760Nm (@weldeiry)

The most important take home message from this @NatureComms study is that if one sees a KRAS wild type #PancreaticCancer please make sure to look for fusions involving alternative drivers (as previously shown by @PancPathologist). Many are actionable. https://t.co/pPD2894Cs2 (@Aiims1742)

◇Strong early signal in CRAF driven NSCLC (KRAS g12v) ◇KRAS WT and and multiple variants KRASm activity in LGSOC (@CrozrX)

Saw a young lady for a 2nd opinion for #PancreasCancer. “BLAND” report. No KRAS (KRAS-Wildtype). We persisted to get repeat tissue for repeat testing that not only had DNA 🧬 but also RNA☀️. ☀️RAF1-FOXP1☀️ fusion. #PANCSM Thoughts? MEK⛔️? https://t.co/uvlLoeQmW1 (@pashtoonkasi)

🔥Extensive analysis on the mutational spectrum of #PancreaticCancer 🔥 @JNCI_Now https://t.co/PdCyLNAtrA ✅16 913pts 👉84.4% KRAS -> 1.6% G12C 👉KRAS WT-> FGFR2 (5.3%), BRAF (13.6%), ERBB2 (6.5%), MDM2 (4.1) IDH1 (4.7%), BRCA1 (1.4%), BRCA2 (3.6%) (@ArndtVogel)

Very important slide from our recent paper on KRAS WT PDAC. Thanks @EileenMOReilly for showing this summary, highlighting the increasing number of targetable alterations in pancreatic cancer. Comprehensive profiling at the DNA and RNA level is critical. #cancer #ESMO22 (@Marindoc)

Excellent study. While results were negative in unselected population, #KRAS wildtype appears to enrich for responders to chemo/IO, mOS 21.7 mo vs 8.8 in KRAS mut. KRAS WT bu #ctDNA looking like predictive biomarker to #immunotherapy in #PancreaticCancer (@BrunoBockorny)

In the burgeoning era of RAS targeted therapies, consider sequencing #PancreaticCancer as a standard of care, but especially don’t miss: A: Rare histological subsets such as the example here B: KRAS wild type (use an assay that interrogates fusions) C: Young onset (<50y) cancers (@Aiims1742)

👏#PrecisionMedicine in #PancreaticCancer by @graokane in @JCO_ASCO https://t.co/XxnAiazHLc ⏳early NGS 👉10% HRD: Platin-CTx/PARPPi 👉10% KRAS WT: more🎯->BRAF, HER2, MDM2, NRG1.. 👉2% KRASG12C Next: RNA profiling, understanding resistance @myESMO @OncoAlert #PrecisionMedicine (@ArndtVogel)

Yes @BenWestphalen. The “WILDTYPE”, whether it’s the RAS/RAF in colorectal cancer or the KRAS-Wildtype in pancreas cancer is enriched in fusions.🧬🧬 Also, important to remember that fusions can also be acquired events. @ASCO @JCOPO_ASCO #CRCSM #ctDNA https://t.co/I6y015OjaR (@pashtoonkasi)

I have a few & we are chasing for FUSIONS.🧬🧬 Imp. RNA is the gold standard to not miss any fusions. Relevant for this #KRAS-wildtype #PancreasCancer #PANCSM. #Cholangiocarcinoma with FGFR. MSI-High➡️NTRK #CRCSM. #WCGIC2022 @myESMO @OncoAlert (@pashtoonkasi)

🤔I have often💭now that we know more about KRAS, should we be re-targeting the EGFR for #PancreaticCancer❓ Dr. Santos & Malcolm Moore👀at the pivotal gem-erlotinib trial, & found a NON-significant⬆️in OS with eroltinib in KRAS WT patients https://t.co/iVALvv05aj (@MPishvaian)

All else being equal, prognosis is best for 1) dMMR colorectal cancer and 2) left-sided KRAS/NRAS/BRAF wild-type without HER2 overexpression. But - prognosis is not destiny. Every situation is different. (@gabe_a_brooks)

Correct - upfront EGFR inhibitor is for left-sided, KRAS/NRAS/BRAF-wild type colorectal cancer without HER-2 overexpression - kind of a mouthful (@gabe_a_brooks)

Multi-line therapy trial in unresectable wild-type #KRAS #NRAS #BRAF metastatic colorectal cancer A GERCOR-PRODIGE randomized open-label phase III study. Excelente presentación por MD. Benoist Chibaudel👏 #ASCO22 #Oncology @OncologyIolc @OncoAlert @ASCO (@Dr_Ivanoncologo)

STRATEGIC-1: Multi-line therapy trial in unresectable wild-type KRAS/NRAS/BRAF metastatic colorectal cancer—A GERCOR-PRODIGE randomized open-label phase III study. Talk by Dr. Benoist Chibaudel, MD #ASCO22 #CRCSM @OncoAlert (@manjuggm)

STRATEGIC-1: Multi-line therapy trial in unresectable wild-type KRAS/NRAS/BRAF metastatic colorectal cancer—A GERCOR-PRODIGE randomized open-label phase III study. Talk by Dr. Benoist Chibaudel, MD #ASCO22 #CRCSM (@manjuggm)

STRATEGIC-1: Multi-line therapy trial in unresectable wild-type KRAS/NRAS/BRAF metastatic colorectal cancer—A GERCOR-PRODIGE randomized open-label phase III study. Talk by Dr. Benoist Chibaudel, MD #ASCO22 #CRCSM (@manjuggm)

STRATEGIC-1: Multi-line therapy trial in unresectable wild-type KRAS/NRAS/BRAF metastatic colorectal cancer—A GERCOR-PRODIGE randomized open-label phase III study. Talk by Dr. Benoist Chibaudel, MD #ASCO22 #CRCSM (@manjuggm)

STRATEGIC-1: Multi-line therapy trial in unresectable wild-type KRAS/NRAS/BRAF metastatic colorectal cancer—A GERCOR-PRODIGE randomized open-label phase III study. Talk by Dr. Benoist Chibaudel, MD #ASCO22 #CRCSM (@manjuggm)

MSS CRC Challenges, Panel discussion #ASCO22 #CRCSM @OncoAlert KRAS WT status? pani+Nivo/Ipi- ~RR 30%, durable response, need explored When CAR-Ts are developed, how are we going to do it? Bi-sp Abs, CAR-Ts, Vaccs, MSS 1 bucket, not good, what can be done better in trials (@manjuggm)