EGFR L858R

ASCO 2023 Plenary abstract LBA3 Dr Roy Herbst lead author of the ADAURA study in EGFRm (ex19del/L858R) stage IB, II or IIIA NSCLC; overall survival benefit of 51% reduction in risk of death in the overall population. #ASCO2023 #precisiononcology #PoetOncology #targetedtreatment (@POETOncology)

It’s not enough to say “EGFR mutation” there are different therapies depending on ex19/L858R vs exon20ins. Have to provide both the street (gene) name and full address as I tell my trainees. Continuation of phenomenal mNSCLC session by ⁦ @riess_md ⁦@HwakeleeMD #MedIQ23ASCO (@MedIQCME)

It’s not enough to say “EGFR mutation” there are different therapies depending on ex19/L858R vs exon20ins. Have to provide both the street (gene) name and full address as I tell my trainees. Continuation of phenomenal mNSCLC session by ⁦@riess_md⁩ ⁦@HwakeleeMD⁩ (@PatelOncology)

3/ 📌 On Dec 18, 2020, the @FDAOncology gave a thumbs up 👍 to osimertinib for adjuvant therapy post tumor resection in NSCLC patients with EGFR exon 19 deletions or exon 21 L858R mutations. ADAURA study showed ➡️ Median DFS not reached vs 19.6 months on placebo (HR 0.17,… https://t.co/zLg1uyLDCc (@ADesaiMD)

NSCLC with an #EGFR exon 20 insertion mutation is different from exon 19 deletion and exon 21 L858R! Drs. Byoung-Chul Cho and @charocampelo describe their approach and Marcia Horn @Exon20Group provides perspective in this episode of #LungCancerConsidered https://t.co/i16OujxoC7 (@StephenVLiu)

Dr. Pasi Janne discusses the current standards with #EGFR NSCLC. Varies by mutation - osimertinib for del19 and L858R but afatinib for uncommon (though osi also active) and amivantamab or mobocertinib for ex20ins. Will we see a shift in the near future to SOC? #RomeLung23 (@StephenVLiu)

2/ @LeXiuning @MDAndersonNews on EGFR mutations: ▪️EGFR mutations ~10-20% NSCLC pts in Europe/N America, & up to 50% of patients in Asia ▪️Exon 19 del & exon 21 L858R most common (~85-90%) ▪️🔑 Most frequent uncommon mutations to know: G719X, S768I, L861Q, & exon 20 insertions (@esinghimd)

My mom's mNSCLC just progressed after 4 years on 1st line osimertinib. A new biopsy showed the original L858R mutation at 6.5%, EGFR copy number 5.3x. What is the best treatment strategy now? Gefitinib cetuximab combination? Thanks. (@love_kb_jun)

🦄 Osimertinib in non-exon 19 deletion or L858R EGFR mutations (excluded from FLAURA trial) Important issue, as they represent ≈ 20% of EGFR mutations in the clinic. Thrilled to participate in this study now @IASLC 🔝 as Editor’s choice @JTOonline #LCSM https://t.co/adB3FJKezV (@Tony_Calles)

Promising efficacy of 4th generation EGFR TKI after 3 weeks in NSCLC pt EGFR L858R, T790M, C797S mutations in progression post gefitinib, osimertinib and amivantamab...to be continued @GustaveRoussy @CICThoraciques (@dplanchard)

Nice talk on EGFR (it’s not enough to just name the street anymore, you have to say the whole address- exon 19 del, exon 20 insertion, L858R etc) in mNSCLC by ⁦@MdCurioni⁩ ⁦@LungSummit⁩ (@PatelOncology)

🧵11 We analyze a large cohort (n=121) of putative tSCLC w/ driver mut typically found in NSCLC ➡️EGFR (ex19del > L858R in SCLC cases!) ➡️ALK ➡️ROS1 ➡️RET ➡️NTRK Need for rebiopsy of all driver+ NSCLC to look for SCLC @EGFRResisters @ALKLungCancer @ros1cancer @RetRenegades (@christine_lovly)

F/66y ,good PS Stg IV Lung with brain mets SRS to brain Exon 21 L858R mut along with Her2 amplification on NGS How to Rx? @LeciaSequist @christine_lovly @DrSteveMartin @drgandara @geoff_oxnard @Alfdoc2 @CharuAggarwalMD @JustinGainor @PatelOncology @VivekSubbiah @Dr_R_Kurzrock (@oncologician)

Masterclass in EGFRx20ins NSCLC with ⁦@RamalingamMD⁩ discussing role for mobocertinib. Not enough to name the gene street anymore (EGFR), we need to house address (exon 19, exon 20ins, L858R, etc). Can determine by NGS either cfDNA or tissue. ⁦@OMIonc⁩ (@PatelOncology)

#ASCO22 Abstract #9006 updates CHRYSALIS-2 cohort of amivantamab + lazertinib in #EGFR NSCLC (del19/L858R) post-osimertinib, post-chemo. In 50pts immediately post osi, RR 36%. In more heavily pretreated (n=56), RR 29%. Full cohort to be reported by Dr. Catherine Shu. #LCSM (@StephenVLiu)

AENEAS: Randomized 1L Phase III Trial of Aumolertinib Vs. Gefitinib in Met. NSCLC With EGFR Ex 19 Deletion/L858R Mut | ⁦⁦@JCO_ASCO⁩ I can’t keep up with all new EGFRi! ⁦⁦@NarjustDumaMD⁩ ⁦@DrMarkAwad⁩ ⁦⁦@CharuAggarwalMD⁩ https://t.co/q4IroZuBe9 (@DrChoueiri)

⭐️ Another new drug for EGFR ✅AUMOLERTINIB 👉🏼AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as 1st-Line Therapy for Locally Advanced or Metastatic NSCLC With EGFR Exon 19 Deletion or L858R Mutations 🧬🎯@JCO_ASCO @OncoAlert https://t.co/ko2T8sUFLh (@VivekSubbiah)

Not sure why PD-L1 <1% is pos and PD-L1>50% is neg. Different than IMP010 & from what we know from other studies. If approved wonder if adjuvant NSCLC landscape,after 4 cycles of platinum: EGFRmt (x19,L858R): osi PD-L1<1%: pembro PD-L1 1-49%: atezo or pembro PD-L1 >50%: atezo (@PatelOncology)

#TTLC22 Dr. @politikaterina reviews acquired resistance to #EGFR TKIs. Similar mechanisms of resistance to osimertinib and 1G/2G TKIs but different frequencies. Interestingly, some resistance mutations seem allele specific - C797S more with del19 and L718 more in L858R. #LCSM (@StephenVLiu)

Interesting discussion here at #gotoWLC regarding situations with multiple drivers. What do you do with a FISH positive ROS1 and EGFR L858R? What do you do with 2 pathogenic EGFR? The panel is leaning into @JoelNealMD for guidance. #LCSM (@KellyMercierPh1)

Mostly included common #EGFR mutations (del19, L858R) but ~5% others. About 35% of patients had brain metastases. Prior TKI required, 30% had two lines of TKI therapy. #ESMOasiaweek21 (@StephenVLiu)

Enrolled 234 pts with EGFR del19 or L858R. All had an R0 resection, 99% with lobectomy, balanced by stage (40% stage II, 60% stage III). Received gefitinib 250mg qday x 2y or 4 cycles of cisplatin + vinorelbine. More G3+ tox with chemo, more rash/diarrhea with gefitinib. #LCSM (@StephenVLiu)

In most #EGFR NSCLC studies, exon 19 deletion associated with better outcomes than exon 21 L858R. This single center analysis explores co-mutations in tumor suppressor genes between the two. Could KEAP1 alterations be playing a role in EGFR mutant NSCLC? https://t.co/FTMW7hF1uV (@StephenVLiu)

#ESMO21 Symposium on #EGFR mutations with Drs. @dplanchard @AlexSpiraMDPhD, Keith Kerr, and Johan Vansteenkiste highlights the differences between del19, L858R, and exon 20 insertions and the evolving treatment landscape. Increasingly complex and increasingly effective. #LCSM (@StephenVLiu)

#ESMO21 Here, 60/40 split of #EGFR del19/L858R. No difference here in PFS. mPFS 20m with osi and 22m with osi/bev. Overall PFS HR 0.862 by BICR. Interesting to contrast to BEVERLY and other erlotinib-based studies. #LCSM @myESMO (@StephenVLiu)

#ESMO21 #LCSM Dr Piccirillo presenting thePh3 BEVERLY-trial: Italian random open-label, trial of bevacizumab (BEV) plus erlotinib (E) vs E alone as 1L treat for EGFR-mut a NSCLC. 180 pts random: 80 vs 80 55% of pts had ex19Del and 41% L858R mutation (@APassaroMD)

Small sample size but interesting report in @JTOonline on 4 patients with de novo T790M/L858R #EGFR NSCLC with acquired resistance to osimertinib. Mechanisms of resistance identified: C797S, C797S/L798I, #MET amp and MTOR L1433S. #LCSM @IASLC @OncoAlert https://t.co/7mg1KB0n8H (@StephenVLiu)

Need help with a #lungcancer patient 66 y/o F , non smoker Stage4- pleural effusion adenoca 2 EGFR mutations EXON 20 c.2303G>T (p.S768I) Exon 21: c.2573T>G (p.L858R) Tx options? Tagrisso? @PatelOncology @JackWestMD @HosseinBorghaei (@BijoyTelivala)

@drharshvardhan @ProfBhargava corona virus behaving like cancer as regards mutations.Egfr L858R lung cancer when treated with Gefirinib, under pressure evolves and develops second mutation T790M after 10 months.Virus evades vaccine by developing new mutants but within weeks. (@drshyam_aggarwa)

It'd be interesting to know the cfDNA VAF of EGFR L858R compared to the others (N-myc amp, p53, PI3KCA), which may shed light on how much lung adeno v. small cell clonality you have. I agree Chemo-Osi sounds more appealing than Chemo-IO (@ChadPecot)

Phase I trial of Osi + Ram in EGFR T90M EGFR MT #NSCLC, 25 pts treated, including those with brain mets. On-therapy loss of EGFR Ex 19 del/L858R, correlated with longer PFS, but on-treatment loss of T790M did not. @CCR_AACR @HelenaYu923 @dplanchard @http://bit.ly/2LpwqWD (@CharuAggarwalMD)

The day of @US_FDA approvals! now osimertinib for ADJUVANT therapy in high-risk NSCLC & EGFR ex. 19 deletions/ ex. 21 L858R mutations test. Efficacy based on ADURA trial (DFS HR 0.17) @JackWestMD @LeciaSequist @DrMarkAwad @drgandara @n8pennell @OncoAlert https://t.co/pca5KJC6y0 (@DrChoueiri)

60/Male Adenocarcinoma of lung pT3N2 (max 4.7cm), R0 Stage IIIB LVI present EGFR L858R+ Took Adj Chemo with Pem+Carbo 4 cycles(Yes Carbo!) Later, Recieved Adj RT (60Gy) Came for adjuvant Osimertinib opinion What is your opinion? @JackWestMD @sujithonco @ChowdaryStalin (@ksivaprasadk)

Really should be clinical trial but if not Chemo/ RT for N2 multistation disease with EGFR L858R and close follow up. Discuss PACIFIC with the caveats clearly explained and honestly would recommend against it as it really does not represent this population well at all 🤷🏽‍♀️#lcsm (@DevikaDasMD)

A colleague asked this Q- i don’t know the answer. It is a Flaw-ADAURA Q. Can #LCSM help? Elderly fit pt with N2 multistation + NSCLC, EGFR L858R. What do we do? @LeciaSequist @n8pennell @JackWestMD @benlevylungdoc @PatelOncology @Alfdoc2 and if he still talks to me @StephenVLiu (@DrSteveMartin)

#ASCO20 The phase III #ADAURA trial included patients with resected stage IB, II or IIIA NSCLC (with or without adjuvant chemotherapy) with an #EGFR deletion 19 or L858R mutation. CNS imaging and post-op CT required before entry. #OncoAlert #LCSM (@StephenVLiu)

Just got call for input on patient with inoperable St IIIA NSCLC who is TOO SCARED to leave the house for CRT!! Turns out tumor is EGFR L858R pos and colleague is considering Osimertinib. Is palliative but I can’t blame him. Expect others have similar challenging cases. (@DrHaigentz)