ALK mutation

🔥🚨@OncoAlert Just out @JTOonline by our team @MayoCancerCare: #CaseReport on a sequential #SmallCell transformation & #ALK I1171T mutation as resistance mechanisms in a pt with #ALK-EML4 #NSCLC treated with combination of #Temozolomide & #Lorlatinib 👇🏼 https://t.co/GkixRkDWr5 (@RManochakian)

ALK Mutation is present in 2.81% of @AACR GENIE cases, with lung adenocarcinoma, colon adenocarcinoma, cutaneous melanoma, breast invasive ductal carcinoma, and endometrial endometrioid adenocarcinoma having the greatest prevalence. https://t.co/xqPTiPcovZ @ALKPositiveinc… https://t.co/KcF0yqWyPP (@4baseCare)

Quite an interesting work by @alexdrilon group. SHP2 does not work by itself, but it seems to restore efficacy of TKIs in heavily pretreated patients, including ALK+ NSCLC and BRAF V600E mutant CRC. @GBOT_Alerta #ASCO23 #LCSM (@MarceloCorassa)

#ASCO23 Abs9003 #LCSM "Final OS analysis of CHOICE-01: Toripalimab + chemotherapy in 1st line advanced NSCLC." ➡️465 pts without EGFR/ALK mutations, toripalimab arm showed significant OS improvement over placebo: HR=0.73 (95% CI: 0.57-0.93), median OS 23.8 vs 17.0 months 🎯.… https://t.co/ZfrJA0cZAm (@ADesaiMD)

Mechanisms of resistance to ALK TKIs are: ALK alterations (mutation and amplification), bypass signal pathways (EGFR/HER3, KIT proto-oncogene receptor tyrosine kinase, KRAS, ILGF-R, M-E-T-HGF, MAPK, and others (E-M-T, P-gp, TP53, transformation to SCLC) https://t.co/oXjoSjwflx (@MLPOncoData)

Dr. @jpmd901 with a great comprehensive discussion of treatment strategies for ALK & ROS1-mutated NSCLC at #TexasLung23. Excellent to see the breadth of therapies in and emerging in this space. @TLCconference (@Joshua_Reuss)

EGFR/ALK/ROS1 mutated/rearranged NSCLC? The suspense is killing us all… (@DrBenKong)

Do recall, in PACIFIC, pts w/ EGFR/ALK mutations were NOT excluded from enrollment -43/713 (6%) pts had EGFR-mutant disease -PFS in this group HR 0.76 (95% CI 0.35-1.64) #lcsm #TTLC23 (@esinghimd)

What happens with ALK NSCLC? On target mutations are monitored by biopsy, but with the 3rd generation, complex ALK mutations present. What to do then? Clin trials for 4th gen ALK TKIs for these complex mutations. @JessicaJLinMD #winterlung (@KellyMercierPh1)

Thx. I’ll try to read it slowly. I ask because I had thought that ALK was a driver, or causative, mutation in lung cancer. Is it just an actionable mutation to attack that was not the cause of the cancer? (@DrdelaCruzMunoz)

Why is there not more excitement for batiraxcept after impressive ASCO data... I am over the moon excited... would love my brother to get access to treat Metastatic NSCLC with ALK mutation, bc AXL is key to its spread. https://t.co/oEdYfRItvY (@dexion10)

Analysis of #lorlatinib analogs reveals a roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancer” by @JessicaJLinMD #AaronNHata #SatoshiYoda #AyaShiba, et al. #alk #positive #research #NSCLC @NatureCancer (@ALK_Research)

But also recognize that in many ALK+ lung cancers resistant to lorlatinib, analysis does not identify on-target resistance with ALK mutations. Effective strategies to target/overcome off-target resistance remains a major challenge and an urgent need. (@JessicaJLinMD)

@DrHendifar @PancPathologist have had success w/ #ALK fusion in metastatic #PDAC following #FOLFIRINOX responsive to #alectinib then acquired alectinib-resistant ALK mutations G1202R and V1180L on G360, then w/benefit to 3rd-gen ALK inh #lorlatinib https://t.co/JnI2dntOfv #pancsm ()

Shout out to my fellow #GIonc crew. Have a young Burmese patient with EMLA-ALK fusion mutation via NGS in metastatic #crcsm, progressing on 2nd line FOLFOXIRI. Very scant data in alectinib in this setting. Anyone with clinical experience? @pashtoonkasi @marklewismd @doctorC369 (@realbowtiedoc)

ALK as another tumor agnostic marker? MyPath pilot for alectinib. Disease control rate = 60% in ALK rearranged including PRs in colon and pancreatic and uterine leiomyosarcoma. No responses in ALK mutated or amplified (@Dr_R_Kurzrock)

Acquired resistance to #ROS1 TKIs explained by Dr. @christine_lovly. Have to consider on-target and off-target mechanisms and just as in ALK, compound mutations present a therapeutic challenge. Emerging drugs showing promise here. #LCSM #TTLC22 (@StephenVLiu)

Going beneath the tip of the iceberg. Identifying and understanding EML4-ALK variants and TP53 mutations to optimize treatment of ALK fusion positive (ALK+) NSCLC https://t.co/Wvv0xjHr0B #ALK #lungcancer #PrecisionMedicine @MNagasaka @ViolaWZhu and Dr. Shannon S. Zhang. (@oncoOuLungCA)

There are a multitude of onc drivers in ALK mutations in #lungcancer says ⁦@AnastasiosDimo1⁩ ⁦@OncLiveSOSS⁩ #ipc with chair ⁦@KArnaoutakis⁩ ⁦@uamshealth⁩ ⁦@MayoCancerCare⁩ how to chose an inhibitor in front line and then how to treat upon progression (@donnashort)

Is there anyone pioneering treatment for clients diagnosed with ALK mutations in non-metastatic NSCLC 3a-b? (@KyleMcnease)

Great work! As a bioethicist looking at things from the outside, can anyone point me towards the rationale for using SOC in non-metastatic NSCLC with ALK mutations until treatment failure before utilizing therapies strictly aimed at stage 4 metastatic NSCLC with ALK mutations? (@KyleMcnease)

Another reminder in #JCOPO @ASCO_pubs that when pathogenic gene fusions are found, they're often viable targets (as this #ALK fusion in breast cancer). Mutations are much more variable so important to note the details when you get your reports. https://t.co/EzCttpWMsP (@StephenVLiu)

■memo Risk of thromboembolism in pts w/ ALK- and EGFR-mutant lung cancer: https://t.co/Xl2tG6Lk1X @JTHjournal @aakonc #CardioOnc Pts w/ ALK-mutant advanced LK have the highest rate of TE. These findings should be taken into consideration in decision-making in pts management. (@OncoCard_Ganken)

Risk of thromboembolism in patients with ALK‐ and EGFR‐mutant lung cancer: A cohort study https://t.co/k5P4GvAWhJ @ALKLungCancer patients had 43% risk of VTE! #LCSM @EGFRResisters @aakonc @VamsiVelcheti (@n8pennell)

Proteasome inhibition may overcome ALK-TKI resistance in ALK-Rearranged/TP53-Mutant #NSCLC @CCR_AACR #LCSM @ALKLungCancer @alk_fusion https://t.co/5sd0lD4f4Q (@CharuAggarwalMD)

New article: #Thrombosis common in non‐small cell lung #cancer pts & ➡️worse outcomes. Roopkumar @MayoClinic et al @aakonc @ClevelandClinic analyse thrombotic events for ALK & EGFR mutant 🧬 subtypes of NSCLC lung cancer pts; ALK mutation 📈 thrombosis https://t.co/udJkqpy0jZ (@JTHjournal)

Our new data re #VTE rates assoc w EGFR and ALK mutations in lung cancer w/ Joanna Roopkumar @poudelmd @GervasoLorenzo @n8pennell @VamsiVelcheti @Keith_R_M @JTHjournal (@aakonc)

#OncoAlert Report in @JTOonline on #ALK NSCLC with 21 patients that underwent biopsy after ALK TKI therapy. Noted several ALK solvent front mutations, SCLC and sarcomatoid transformation. Included several novel ALK mutations as well. #LCSM @IASLC https://t.co/Prt6Eb3QpU (@StephenVLiu)

Enjoyed the impt NACLC20 Oral Abstract on Real-world PFS in oncogene driver-mutated NSCLC treated w single-agent IO. KRAS mutations stand out as different from EGFR/ALK, but more similar to BRAF mutants. Limitation: Line of Rx not known. (@PatrickCMa1)

#OncoAlert Report @JTOonline @IASLC on phase II #ATOMIC study of brigatinib in #ALK NSCLC after next-gen ALK TKI therapy. RR 40%, DOR 5.3m, mPFS 7m. Responses seen with ALK resistance mutations (G1202R, I1171T, L1196M). @rdoebele @HornLeora #LCSM https://t.co/aoWJ1Gu0NP (@StephenVLiu)

Liquid biopsies! The reason my husband is still farming 700 acres by himself, 5 years after his stage 4 lung cancer diagnosis. Liquid biopsy found the ALK mutation at diagnosis and the G1202R mutation at progression & both led to a decisive treatment plan. Thank you #harvest2020 (@RhondaMeckstro1)

#ASCO20 Response to brigatinib (post-alectinib) noted in the presence of various #ALK resistance mutations including G1202R (1/3), L1196M (3/3), I1171N (1/2), I1171S (1/1). Well tolerated. Most common G3 tox were lipase (no pancreatitis), CK (no myalgias), HTN. #OncoAlert #LCSM (@StephenVLiu)

@Jbauml @StephenVLiu . In looking at #COVID19 in #lcsm @ #AACR20, was any data presented on egfr/alk/ros mutation? Is it truly lung cancer that was the risk factor or was lung cancer a surrogate for pre-existing lung disease? (@SyedMAhmedMDPhD)

"Great collab @GustaveRoussy @CLCCLeonBerard 💉 ctDNA is clinically relevant for our #ALK #ROS1 #NSCLC patients. One example: at 2ndG-TKI failure, we detected 29% ALK resist. mutations. Will we guide TKI therapy by ctDNA? 🙂@AurelieSwalduz @BenjaminBesseMD & P. Saintigny @Inivata" (@LauraMezquitaMD)

Great collab @GustaveRoussy @CLCCLeonBerard 💉 ctDNA is clinically relevant for our #ALK #ROS1 #NSCLC patients. One example: at 2ndG-TKI failure, we detected 29% ALK resist. mutations. Will we guide TKI therapy by ctDNA? 🙂@AurelieSwalduz @BenjaminBesseMD & P. Saintigny @Inivata (@LauraMezquitaMD)