Stephen V Liu, MD Profile picture
Sep 19, 2020 11 tweets 11 min read Read on X
#ESMO20 Eagerly awaited presentation by @peters_solange on consolidation nivolumab and ipilimumab (vs observation) for patients with LS-SCLC after chemoradiation: ETOP/IFCT 4-12 STIMULI trial #LCSM @OncoAlert @myESMO Image
#ESMO20 While we have adopted IO for ES-SCLC, its role in LS-SCLC is not yet known, though outcomes in LS-SCLC are still poor. Nivo/ipi has activity in SCLC, but note that the consolidation/maintenance approach in ES-SCLC was not successful. #LCSM ImageImage
#ESMO20 Study design outlined here: enrolled at diagnosis or after 1 dose of chemotherapy to allow referrals (smart design). Standard concurrent CRT followed by 1:1 IO vs observation. Used nivo 1mg/kg and ipi 3mg/kg q3w x 4 cycles with maintenance nivolumab (not low dose ipi). Image
#ESMO20 Statistical design including explanation of premature closure to accrual which led to a pretty long period of accrual. Treatment failure in observation was due to progression whereas in nivo/ipi arm, it was toxicity. ImageImageImage
#ESMO20 Consolidation nivo/ipi after chemoradiation for LS-SCLC did NOT improve PFS. HR 1.02 with curves crossing multiple times. Median PFS for nivo/ipi was 10.7m versus 14.5m for observation. #LCSM @OncoAlert Image
#ESMO20 Subgroup analysis without clear trends to identify groups that would benefit from nivo/ipi consolidation. Patterns of progression similar, mostly new lesions. #LCSM @OncoAlert ImageImage
#ESMO20 Consolidation nivo/ipi after concurrent chemoradiation for LS-SCLC did not improve survival with an OS HR 1.06. Interesting approach looking at piecewise hazard ratios and this may mature differently but as of now, no OS benefit. #LCSM Image
#ESMO20 Disappointing OS results with nivo/ipi consolidation. Subgroup analyses here not very telling. More toxicity with nivo/ipi, naturally, vs observation, but nothing unexpected. #LCSM ImageImageImageImage
#ESMO20 Overall, the use of consolidation nivolumab and ipilimumab after concurrent chemoradiation for LS-SCLC did not improve PFS or OS. Longer follow up may inform late impact, though crossover at relapse may make that challenging. #LCSM @OncoAlert @myESMO ImageImage
#ESMO20 My immediate reaction is disappointing as there is a lot of rationale for IO post CRT in LS-SCLC. Is it the ipi - is the dose too high in a population with co-morbidities (worsened by CRT)? Parallels to CheckMate 451 (maint nivo/ipi in ES-SCLC did not improve OS)? #LCSM Image
#ESMO20 This question of IO post CRT for LS-SCLC is still valid (better without CTLA4?). Consider referring to NRG-LU005 (chemoradiation +/- atezolizumab, NCT03811002) or ADRIATIC (chemoradiation followed by durva +/- treme, NCT03703297). #LCSM

clinicaltrials.gov/ct2/show/NCT03…

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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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