PD-L1 overexpression

🚨Very high PD-L1 expression (>90%), high TMB, and increased CD8+PD1+ T cells density associate w/ prolonged benefit from CRT ➡️durvalumab in stage III #NSCLC. Out in @NatureComms our multi-center analysis led by🌟 @alessi_joao. #biomarkers can help⬆️outcomes. @OncoAlert #LCSM (@BiagioRicciutMD)

5/8 In examining clinical outcomes to PD-(L)1 based therapies, there was no difference between patients with ATM mutant and ATM wild-type NSCLC, despite increased TMB/PD-L1 expression (though higher rate of KRAS/STK11 co-mutations) in the ATM mutant subset. (@BiagioMd)

6/8 By contrast, concurrent ATM/TP53 mutations were associated with increased TMB, high PD-L1 expression, and improved ORR and PFS with PD-(L)1 blockade in patients NSCLC. (@BiagioMd)

Congratulations! Very high PDL1 expression in 1/3 of RET-NSCLC can mislead clinicians to use IO upfront therapy, which is ineffective and therefore contraindicated here (@GautschiOliver)

💡one fun fact that I recently learnt. The reason why PD-L1 expression is very high in #EBV associated gastric cancer is that the virus 🦠 simplistically grows through the PD-L1 highway 🛣. So technically your non-MSI that has a high ⬆️CPS gastric cancer would be your EBV➕. (@pashtoonkasi)

What is your threshold of high PD-L1 expression for prescribing single-agent immunotherapy in 1L advanced NSCLC? Review the data from a trial that enrolled advanced NSCLC patients with PD-L1 ≥50% here: https://t.co/wEx0TbqbZq #SponsoredByRegeneron (@edgardo_ny)

Prevalence of PD-L1 high expression in advanced #UrothelialCarcinoma: results from the #PREVAIL prospective cohort study. Presentation by @PGrivasMDPhD @UW. #ESMO22 written coverage by @WallisCJD @UofT on UroToday > https://t.co/TPRPJsffBD @myESMO (@urotoday)

Capmatinib Plus Pembrolizumab Does Not Provide Clinical Benefit in MET Unselected, PD-L1-high Expressing NSCLC @TonyMok9 @ASCO #ASCO22 #lcsm https://t.co/AAYycXEh1y (@OncLive)

During a live virtual event, Ravi Salgia, MD, PhD, discussed the use of immune checkpoint inhibitor monotherapy for a patient with non–small cell lung cancer with very high PD-L1 expression with participants. #nsclc #lcsm @DrRaviSalgia @cityofhope https://t.co/SfAmDTLkVr (@TargetedOnc)

Report @LungCaJournal that high PDL1 expression in #ALK NSCLC associated with worse outcomes. #PDL1 high (23% of pts) had shorter PFS and shorter OS. Surrogate for specific variants or co-mutations? This does not equate to immunotherapy efficacy though! https://t.co/mlHbOmSChK (@StephenVLiu)

Atezolizumab shows little heterogeneity in efficacy in high PD-L1 expressers with stage II–IIIA NSCLC #ELCC22 #LCSM https://t.co/vlv5oYCHtJ (@n8pennell)

#TTLC22 In P09, Dr. Yunan Nie reports high PDL1 expression in patients with #ALK NSCLC linked to worse prognosis on ALK TKI. No difference in RR but PFS much shorter in PDL1 high (14m) vs PDL1 low/neg (54m). Prognostic power, but biologically, how is PDL1 linked to resistance? (@StephenVLiu)

Phase II study of atezolizumab with bevacizumab for non-squamous non-small cell lung cancer with high PD-L1 expression (@Be Study) | Journal for ImmunoTherapy of Cancer https://t.co/iUceXrvjnB (@VivekSubbiah)

#LungCancer - Most Viewed Reviews, 2021 ⭐ #2: A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With #NSCLC and High PD-L1 Expression 👨‍⚕️👩‍⚕️@DrRoyHerbstYale) et al. Read here 👉 https://t.co/d9mp5vCiUK @YaleCancer #LCsm (@FrontOncology)

Enjoyed the stimulating discussion with @PGrivasMDPhD @tompowles1 @sonpavde : most important messages 👉tumor PD-L1 expression is highly "unreliable" & platinum chemo (followed by avelumab maintenance) remains the most favored treatment for most pts with advanced #bladdercancer (@neerajaiims)

MORE w/ #ASCO21 abstract released today: Landscape of KRASG12C, associated genomic alterations, and interrelation with immuno-oncology (IO) biomarkers. Relationship to high TMB and PD-L1 overexpression. #Colorectal #CRCSM @agrothey @JeanneTie https://t.co/9D9lPl59AJ (@fireflyann)

Is PD-L1 expression higher in HER-2 positive gastric cancer? Or is there another explanation for “synergism”? Exciting for sure - will be intrigued to learn more. (@gabe_a_brooks)

The Onco-Onion News in Brief: BMS, Investigators ‘thrilled’ at improving OS in all gastric cancer patients with immunotherapy Today the FDA approved nivolumab for first line therapy with chemotherapy. “While we are pleased about the high PDL1 expressers, we are most (@DocCatenacci)

Great to have an FDA-approved option for high PDL1 expressing tumors of the esophagus and GEJ with chemo+pembro in first line setting - where it should be used. @OncoAlert (@DocCatenacci)

5/5 Oncogene addicted NSCLC are characterised by low TMB + less inflammatory tumour microenvironment+poor tumour-infiltrating lymphocytes. PD-L1 can be overexpressed without having any clinical significance @OncoAlert @Alfdoc2 https://t.co/BSh1H3THzW (@VivekSubbiah)

As PI in the EMPOWER Lung 1 trial, I’m happy with FDA Approval to Cemiplimab-rwlc for Patients With NSCLC and High PD-L1 Expression - The ASCO Post https://t.co/UGOqGi8kne @ASCO @JGO_ASCO @GlopesMd @FroitbergM @EricTopol @GBOT_Alerta @mab_sp125 @NicoleRossiOnco @vencerocancer (@cassilandense)

KRAS G12C (vs other KRAS mutations) were more likely to have lymphovascular invasion and had a higher #TMB (with more STK11 and NF1 mutations). KRAS also more likely to have high PDL1 expression (37% in KRAS G12C, 35% in KRAS other, 25% in KRAS WT). #LCSM @kRasKickers (@StephenVLiu)

Your patient w/adv non-squam NSCLC, no driver mut'n, & high PD-L1 express'n has had a good PR, still residual primary tumor, several smaller but still enlarged LNs, & a few met foci in bones, more sclerotic now. What do you recommend after 2 yrs if no restriction from payer? (@JackWestMD)

Steroid Use Independently Predicts for Poor Outcomes in Patients With Advanced NSCLC and High PD-L1 Expression Receiving First-Line Pembrolizumab Monotherapy https://t.co/Sv8PN6Ykzz (@AndresFCardonaZ)

KEYNOTE-062 trial in loc adv gastric/GE jxn cancer shows 1st line pembrolizumab is non-inf to chemo w/greater tx effect in pts w/MSI-H or high PD-L1 expression (CPS >10) & no meaningful benefit of pembro+chemo observed https://t.co/8NQCYRfefG @KoheiShitara #VisualAbstract #GICSM (@JAMAOnc)

IMpower110: Atezolizumab monotherapy resulted in longer overall survival (20.2 vs. 13.1 months) than platinum-based combination chemotherapy among patients with previously untreated metastatic NSCLC with high PD-L1 expression @OncoAlert @DrRoyHerbstYale https://t.co/RTXW194P2I (@jesusanampa)

The presence of MSI-H by IHC must be validated by NGS, it is a rare and almost exclusive condition for carcinoids and SCLC. The NSCLC BRAF+ that respond to IO are usually non-V600E, the V600E tend to have equivocal H-PDL1 due to IFN overexpression. I used BRAF targeted therapy 1L (@AndresFCardonaZ)

KEYNOTE-062 trial in loc adv gastric/GE jxn cancer shows 1st line pembrolizumab is non-inf to chemo w greater tx effect in pts w/MSI-H or high PD-L1 expression (CPS >10) & no meaningful benefit of pembro+chemo observed https://t.co/q4pnfUU8Fu @KoheiShitara #GICSM #VisualAbstract (@JAMAOnc)

The updated ORR and PFS are presented here, noting an increase in ORR. Difference seems amplify with PD-L1 overexpression. Surprising - why should PD-L1 lead to TIGIT working better. I would note that the ORR to atezolizumab alone in this group seems low. #ASCO20 #LCSM (@Jbauml)