Discover and read the best of Twitter Threads about #esmo22

@ZPiotrowskaMD

Dr. @ZPiotrowskaMD presents initial results from the ELIOS trial at #ESMO22 - molecular profiling of #EGFR mutant NSCLC after progression on 1L osimertinib.

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

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

German Biotech

@GermanBiotech

1/n
I'm looking at $LPTX right now and trying to understand the stock price drop following #ESMO22.
There is actually little change in the data compared to previous ASCO-GI 2022 data.
If you do a more rigorous evaluation on an ITT basis and count only confirmed responses,

2/n
the ORR is 52% and is not much greater than the ORR of nivo + chemo (47%) or tisle + chemo (47%). However, the mPFS is significantly greater (11.3 mo vs 7.7 mo and 6.1 mo, resp.). mOS has not been reached after a median study duration of 15.7 mo (nivo + chemo mOS =13.8 mo).

3/n
Subgroup analysis is too complicated for a Twitter posting because of different, sometimes opposing influences, but does not change the summary.
Perhaps it irritated the investors that mPFS of DKK-high group (11.3 mo) is smaller than the mPFS of the DKK-low group (12.0 mo).

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#ESMO22 final Presidential Symposium III presentation, #IPSOS, evaluating atezolizumab vs single-agent chemotherapy in pts with advanced NSCLC unsuitable for 1L standard platinum-based chemotherapy, N=453, primary EP: OS

#ESMO22 #IPSOS with a median f/u of 41 mo, atezolizumab monotherapy resulted in significantly improved OS (mOS: 10.3 vs 9.3 mo; HR-0.78; P=.028). The improved was seen across subgroups and independent of PD-L1 expression

#ESMO22 #IPSOS ORR (16.9% vs 7.9%) and DOR (14.0 vs 7.8 mo) were better with atezo, but no significant difference in PFS was found

@MLJohnsonMD2

#ESMO22 Presidential Symposium III continued with the eagerly awaited #CodeBreak200 evaluating sotorasib vs docetaxel in pts w/ locally advanced or metastatic KRAS G12C-mutated NSCLC (N=345) presented by @MLJohnsonMD2 from @SarahCannonDocs

#ESMO22 #CodeBreak200 met it's primary EP of improved PFS by BICR with a median f/u of 17.7 mo. Median PFS: 5.6 vs 4.5 mo, HR=0.66, P=.002

#ESMO22 #CodeBreak200 ORR was higher in pts treated with sotorasib (28.1 vs 13.2%) and mDOR was longer with sotorasib (8.6 vs 6.8 mo). There was no difference in OS

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@DrChoueiri

#ESMO22 COSMIC-313 presented by @DrChoueiri Triplet therapy with cabo/nivo/ipi vs cabo/nivo for patients with advanced TN advanced intermediate or poor-risk #RCC. Primary EP: PFS; N=855

#ESMO22 #COSMIC313: Longer PFS with triplet vs doublet. mPFS NR vs 11.3 mo with benefit seen in most predefined subgroups #RCC

#ESMO22 #COSMIC313 ORR 43% vs 36% with 3% CR in both arms; mDOR not reached in either arm #RCC

German Biotech

@GermanBiotech

1/n

#ESMO22

▪ ZW49 $ZYME seems well tolerated, however, unexpected is the alopecia (→ the linker would need a closer look).
▪ The dose needs to be increased (T-DXd is dosed much higher).
▪ The efficacy data (ORR, DCR) at 2.5 mg/kg 3QW in ≥ 3L mBC are very weak,

2/n

but those in ≥ 2L GEA are surprisingly about as good as T-DXd at 6.4 mg/kg 3QW.
▪After 3 years of phase 1, the overall data situation is very thin.

3/n

After reading through the transcript of the CC, I cannot understand the $ZYME Mgtm's rationale for moving ZW49 forward.
For example, in the 3L mBC indication, 1.5 mg/kg 3QW ARX788 $AMAM achieves 66% ORR and 5.4 mg/kg T-DXd $AZN achieves 61% (median 6 pretreatments in each

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Federico Pio Fabrizio

@FPFabrizioPhD

L'inquinamento atmosferico può causare il cancro ai polmoni nelle persone che non hanno mai fumato? Com'è possibile? C'è un nuovo meccanismo biologico/molecolare alla base. Un thread (lungo ma spero interessante) per parlarvene 1/n 🧵

Sì, è stato identificato un nuovo meccanismo attraverso il quale particelle inquinanti molto piccole nell'aria possono innescare cancro ai polmoni in persone che non hanno mai fumato, aprendo la strada a nuovi approcci di prevenzione e sviluppo di terapie da #ESMO22. 2/n

Si tratta di uno studio realizzato dagli scienziati del Francis Crick Institute, in particolare dal prof. Charles Swanton e dal suo team insieme all'University College di Londra. Parliamone. 3/n

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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

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@marinagarassino

Dr. @marinagarassino presents 5-year efficacy and safety update of KEYNOTE-189 (1L carboplatin plus pemetrexed +- pembrolizumab in non-squamous NSCLC) #ESMO22

KEYNOTE 189 is our SOC and has shown a consistent benefit including improving OS even with a crossover rate of 57%. #ESMO22

KEYNOTE 189 shows sustained OS benefit with longer follow up and a 5y OS rate of 18.4% with an OS HR of 0.60. Better PFS and OS also observed. Benefit across PDL1 strata. No new safety signals . #ESMO22

Dr. Baohui Han presents SUNRISE: randomized phase II study of sintilimab (PD1) and anlotinib (anti-angiogenic TKI) in metastatic NSCLC. #ESMO22

Study design here shows randomization to first-line sintilimab + anlotinib or chemo (with sintilimab at progression). Some concerns about randomization to chemotherapy without immunotherapy in a modern day study. #ESMO22

Baseline characteristics show a fairly high proportion of never smokers. SUNRISE excluded EGFR, ALK, and ROS1 - would like details on testing methods and presence of other drivers. More pts with brain and liver metastases in the sintilimab + anlotinib arm. #ESMO22

@LauraMezquitaMD

Dr. @LauraMezquitaMD discusses the DESTINY-Lung02 data at #ESMO22

Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate (ADC) targeting #HER2 and in DESTINY-Lung01, RR was encouraging at 55% but some concern for toxicity (adjudicated drug-related ILD in 26% of cases). #ESMO22

In DESTINY-Lung02, we have a randomization of pts with #HER2 mt NSCLC (with prior therapy) to the 6.4 mg/kg dose used in DESTINY-Lung01 or a lower, 5.4 mg/kg dose. RR higher at 5.4 (due to maintained intensity from less tox? or imbalance in baseline characteristics?) #ESMO22

Dr. Koichi Goto starts the lung mini oral session with results from DESTINY-Lung02 of the recently approved trastuzumab deruxtecan in #HER2 NSCLC #ESMO22

DESTINY-Lung02 compared two doses of trastuzumab deruxtecan (T-DXd) in #HER2 previously treated NSCLC (5.4 mg/kg vs 6.4 mg/kg): RR 58% and DoR 8.7m at the lower dose compared to 43% at 6.4 mg/kg. #ESMO22

Importantly- interstitial lung disease much less frequent at the 5.4 mg/kg dose (5.9%, only 1 case of G3). This is the FDA approved dose of trastuzumab deruxtecan in #HER2 NSCLC #ESMO22

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@NReguart

Discussant Dr. @NReguart reminds us of the heterogeneity of stage III NSCLC and our teaching has been to determine resectability before treatment. The INCREASE study starts to challenge that. #ESMO22

The difference here is radiation and in T3/T4 NSCLC, local control is so critical. Largely unexplored to date. The INCREASE study explores quad-modality therapy and the results were quite impressive. High pCR rates and seen across PDL1 strata, not just in PDL1 high. #ESMO22

#ESMO22 High G3 TRAE rates but note that use of platinum + etoposide was common and many of these may have been paper toxicities. Any grade pneumonitis only 11% (note radiation dose was usually 50 Gy).

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Dr. Eddie Garon presents data from CANOPY-A - adjuvant canakinumab for resected NSCLC #ESMO22

Canakinumab in the CANTOS study was associated with a reduction in NSCLC incidence. Led to CANOPY-A: large study of adjuvant canakinumab after surgery and chemotherapy for NSCLC. #ESMO22

Adjuvant canakinumab did not improve DFS (HR 0.939). CANOPY-A clearly a negative study. #ESMO22

Dr. Idris Bahce presents data from the INCREASE trial - ipilimumab plus nivolumab and chemoradiation followed by surgery in resectable and borderline resectable NSCLC. #ESMO22

Focus is on high T stage and low N stage - not resectable initially but potentially resectable after therapy. Patients here received nivo/ipi on day 1 and nivo on day 22 with chemoradiation then resection 6w later (after restaging) with pCR/MPR primary endpoint. #ESMO22

#ESMO22 Patient disposition here - of 26 patients who completed induction therapy, 3 are still on therapy and 24 completed surgery. Included 66% T4 and 59% N0 (only 13% N2). Majority (63%) had PDL1 high disease. There was one G5 AE (COVID). No AE prevented surgery.

@DrSanjayPopat

Dr. @DrSanjayPopat expertly discussing the ADAURA update #ESMO22

@DrSanjayPopat

@DrSanjayPopat @myESMO #ESMO22 @DrSanjayPopat points out that the DFS HR is on par with the original analysis but the shape of the curves is different, especially for stage II/III

This is not new - we see a rise in recurrence once TKI is stopped in multiple other adjuvant TKI studies. Is this suggestive of cure or just proper therapy of unidentified (micro)metastatic cancer? #ESMO22

Professor Masahiro Tsuboi presents an important update on ADAURA (adjuvant osimertinib for #EGFR NSCLC) #ESMO22

The DFS HR of 0.23 in resected stage II/III remains very impressive. But once osimertinib is stopped after 3y, the curves do seem to be coming closer together. DFS at 2y with osi is 90% and at 3y is 84% but drops to 70% at 4y. Are we preventing recurrence or delaying it? #ESMO22

#ESMO22 in the overall population, similar trends. Off therapy, DFS curves start to approach. Same trends across stages - though I feel more noticeable in stage III (using AJCC 7 or 8).