Stephen V Liu, MD Profile picture
May 8, 2020 7 tweets 7 min read Read on X
#OncoAlert Report @JTOonline on PDL1 variability in metastatic #NSCLC. A lot of intriguing information on this increasingly imperfect biomarker. Important to understand what's driving the heterogeneity and how it impacts treatment. @IASLC #LCSM

jto.org/article/S1556-…
#OncoAlert In an analysis of 1398 patients with NSCLC they looked at patterns of PD-L1 expression and the impact of disease site and prior therapy. In a subset who received checkpoint inhibitors, they also looked at outcomes. Could influence how we look at PDL1 IHC. #LCSM
Lesson 1: PD-L1 varies by site. Previously reported. If the biopsy is from liver or adrenal, PDL1 runs higher. Brain and bone, PDL1 tends to be low. Some sets have small numbers but interesting trends and may reflect differences in the immune microenvironment #OncoAlert #LCSM Image
Lesson 2: High PDL1 more common in tumors w/ #ALK fusions, #MET amp, #BRAF V600E, #RET fusions. We have to remember that PDL1 in the context of a driver alteration means something different. Since PDL1 IHC comes back quickly, we have to be patient and wait for NGS results! #LCSM
Lesson 3: Treatment may influence PDL1. 77 patients had paired biopsies with interval treatment. Half had a major change in PDL1. Prior IO therapy led to a major decrease in PDL1 in ~40% of patients. Trends persist even when same organ biopsied. #OncoAlert #LCSM
Lesson 4: Predictive value of PDL1 may vary by site. This is interesting: high PDL1 expression in biopsies from lung or distant metastases correlate with response (left) and survival (right). High PDL1 from lymph node biopsy was NOT associated with RR, PFS or OS! #OncoAlert #LCSM ImageImage
Perhaps we need to consider source of tissue when interpreting PDL1? If I have tissue from lung and lymph nodes, should I be testing the lung biopsy for PDL1? Perhaps send nodal tissue for NGS and save lung tissue for PDL1? Yet another variable to consider! #LCSM @IASLC Image

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More from @StephenVLiu

Sep 8
Dr. @marinagarassino at #WCLC24 Presidential Plenary presents Normalized Membrane Ratio of TROP2 as a biomarker for datopotamab deruxtecan in TROPION-Lung01 (Dato-DXd vs docetaxel in previously treated NSCLC which previously showed PFS benefit with Dato-DXd.


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#WCLC24 TROP2 IHC has been a poor predictive marker. Normalized Membrane Ratio (NMR) factors in receptor internalization. Ratio is membrane expression over membrane plus cytoplasmic expression (using optical density from digitized slide) and lower would be more favorable.

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#WCLC24 TROP2 QCS-NMR seems to be a much better predictor of benefit with datopotamab deruxtecan in BEP and in non-sq non-AGA subset: in NMR+, PFS HR 0.57 and KM shows clear separation.
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Read 4 tweets
Apr 23, 2023
Dr. Shun Lu presents interim results from the perioperative NEOTORCH study at the #ASCOPlenarySeries. Randomized pts with resectable stage II/III NSCLC to perioperative chemotherapy with toripalimab (anti-PD1) vs placebo. Another entry in the perioperative space? #LCSM Image
Includes resectable stage II/III (AJCC v8), EGFR/ALK wild type NSCLC. Pts receive 3 cycles of neoadjuvant chemotherapy + toripalimab vs placebo then surgery then 1 more cycle of adjuvant chemo (+tori/pbo) then 13 doses of maintenance toripalimab vs placebo. #ASCOPlenarySeries Image
First interim EFS analysis only for stage III. Includes 404 pts - but 926 screened. Would be interesting to see specific eligibility criteria not met in screening process. Reminder of how selected trial populations are and value of future real-world analyses. #ASCOPlenarySeries ImageImage
Read 11 tweets
Apr 16, 2023
Impressive data from #AEGEAN at #AACR23 from Dr. John Heymach and colleagues. This is the first of several phase III peri-operative IO studies in resectable NSCLC combining neoadjuvant chemo-immunotherapy followed by adjuvant immunotherapy. Image
Included stage IIA-IIIB (AJCC v8) with no EGFR/ALK & excluded pts who would require pneumonectomy. Large study with n=801 (CM816 was n=358). Pts received 4 cycles (not 3) of platinum-based chemo with durvalumab (anti-PDL1) or placebo, then surgery, then durvalumab / placebo x 1y. Image
Almost 75% received carboplatin over cisplatin. Global study; fairly even PDL1 distribution. 80% of pts went to surgery, 78% completed resection (90-95% of those were R0). Overall, 66% of pts began adjuvant phase (but 90% of those who had an R0 resection had adjuvant therapy). ImageImageImage
Read 9 tweets
Dec 8, 2022
There is a lot to consider in this first-line study of the #KRAS G12C inhibitor adagrasib plus pembrolizumab from #ESMOImmuno22. Some pleasant surprises in terms of safety. Definitely encouraging but need to see a bit more to be sold on this strategy. 🤔 #LCSM Image
We're looking for synergy with the two agents - more than an additive effect. Reason to believe there will be based on preclinical data showing the effect on T-cell infiltration from #KRAS inhibition. Similar to what has been shown with MEK inhibition. #ESMOImmuno22 Image
The first-line dataset includes the phase Ib KRYSTAL-1 and the phase II KRYSTAL-7. In KRYSTAL-1 (n=7), 4/7 had a response and all were durable (>9m). G3 TRAEs in 4 pts (lipase elevation, LFTs, muscular pain, pneumothorax). #ESMOImmuno22 ImageImage
Read 10 tweets
Sep 19, 2022
Dr. @ZPiotrowskaMD presents initial results from the ELIOS trial at #ESMO22 - molecular profiling of #EGFR mutant NSCLC after progression on 1L osimertinib. ImageImage
In this study of highly motivated pts at esteemed sites, evaluable paired biopsy at PD only available in 46/115 pts (40%). Interestingly, 75 pts (65%) had paired biopsy but 27 failed NGS (23%). Speaks somewhat to the real world feasibility of a repeat biopsy approach. #ESMO22 Image
Common co-mutations at baseline included TP53, EGFR amp, and CDKN2A loss. Acquired alterations included MET amp, EGFR C797S, ALK fusion, NKX2-1 amp. Mostly mutually exclusive. #ESMO22 ImageImageImage
Read 5 tweets
Sep 11, 2022
Dr. Silvia Novello presents 5y update on KEYNOTE 407 (platinum plus tax and +/- pembrolizumab for 1L squamous NSCLC #ESMO22
With longer follow up, OS favors pembrolizumab arm with mOS 17.2 vs 11.6m (OS HR 0.71) in squamous NSCLC. 5y OS rate 18.4% vs 9.7%. PFS benefit (HR 0.62) and higher RR across PDL1 strata. #ESMO22
For patients who complete 2y of pembrolizumab, 3y OS rate (after completing 2y pembro) was 70% - though not all of those patients are cured (44% were alive without PD or subsequent therapy). #ESMO22
Read 4 tweets

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