In the phase 2 HUDSON study, patients with advanced non-small cell lung cancer received anti-PDL1 combined with biomarker guided therapies, leading to benefit in response to the combination ATR kinase inhibitor ceralasertib + durvalumab Benjamin Besse nature.com/articles/s4159…

Ceralasertib (ATR kinase inhibitor) for 7 days + durvalumab q4w: a promising combo post chemo-IO in pts with advanced NSCLC! nature.com/articles/s4159…. Benefit seen in all comers, including ATM altered NSCLC & manageable safety. Currently tested vs docetaxel in the trial Latify.

Drug access is a major issue. In the phase II study EORTC LCG-163 APPLE, similar OS (HR 1.01) for gefitinib (now a generic drug) followed by osimertinib vs osi in pts w advanced EGFR-mut NSCLC. Less brain PD with Osi vs the sequential strategy (HR 0.54) ascopubs.org/doi/10.1200/JC…

Metastatic cancers should be classified as much as possible based on their biology, and agnostic of organ of origin
To reach this vision, new statistical tools are needed to claim that drugs work across multiple cancers
TY nature & Lucy Odling-Smee for the opportunity to write about it

Le professeur Benjamin Besse et le docteur Antonin Levy présentent le DU de carcinologie thoracique intégrée - CICT de Gustave Roussy et Faculté de Médecine Paris-Saclay. Une formation centrée sur la prise en charge des tumeurs thoraciques

Inscriptions : tinyurl.com/36nym63h

Non G12C KRAS update
The new KRAS inhibitors are there! 1st results from phase I
⁃ panRAS inhibitor (all G12x) RMC 6236 - ORR 38% in NSCLC
⁃ G12D inhibitor HRS 4642 - 1 PR / 8 pts and some tumor reduction (dose escalation ongoing)
Great discussion by Elena Garralda #ESMO23

Sabestomig (AZD7789) is a bi-specific PD-1/TIM3 antibody that demonstrates activity in IO-experienced patients with NSCLC. The dose escalation part of our phase I shows that it is safe, with 30% mostly low grade immune mediated AEs, and no DLT. #ESMO23

Very elegant slide from FLAURA2 by d.planchard. It highlights, for the osimertinib+chemo arm:
- transient toxicities of chemo
- potential tachyphylaxia for osi (some symptoms improve spontaneously)
- low grade long lasting toxicities that are rarely properly reported. #ESMO23

Randomized non comparative phase II whois(L,3)(💙,🧡)🛸❤️ .fuel💙 De.Fi Army🐉 $MON RTEP7. During chemo-radiotherapy, a petscan after 42 Gy helped to plan a boost (66 to 74 Gy) when there was a residual uptake. This strategy improves local control and OS, without additional toxicities. #ESMO23

KN671, perioperative pembrolizumab improves EFS AND OS, at least in pts with PD-L1 1%+ stage II/III NSCLC. Role of the (expensive) adjuvant component and long term toxicities are still unknown. Hope it will convince payers so that academics can start de-escalation trials. #ESMO23

ESMO LBAs!
-ALINA adj alectinib HR DFS .24
-PAPILLON 1L Ct-amivantamab vs Ct in EGFR Ex20 HR PFS .40
-LIBRETTO-431 1L selperca vs Ct-IO in RET+ HR PFS .46
-CM77T periop nivo HR EFS .58
-MARIPOSA 1L ami-laz vs osi in EGFRmut HR PFS .70
-TROPION 2L+ Dato-DXd vs docetaxel HR PFS .75

With immunotherapy before/after the resection of a primary lung cancer, we seek to improve OS by reducing the risk of recurrence. Do we also prevent the risk of other tobacco induced cancers (second primary lung, bladder, head and neck…) ? ejcancer.com/article/S0959-…

In 66 pts with NSCLC and RET fusions, 32 (48%) experienced at least one thromboembolic event including 19 (29%) pulmonary embolism and 10 (15%) ischemic stroke. Trials with preventive treatment needed. Mihaela Aldea Arianna Marinello, MD RETpositive
jamanetwork.com/journals/jamao…

Phase III trial on cancer vaccine OSE2101 versus CT in HLA-A2-positive pts (prevalence 45%) with advanced NSCLC post CT & IO. Early discontinuation (COVID) but OS benefit in the subgroup with secondary resistance to IO. To be confirmed in a new trial! annalsofoncology.org/article/S0923-…

CTLA-4 matters for PD•L1 neg NSCLC! In this subgroup, ipilimumab+nivolumab is associated with more long term survivors whereas chemo alone vs chemo-nivo or chemo-pembro have very similar 5 year survivals. #WCLC2023
All curves displayed here are in PD-L1 neg subgroups.

Accumulative publications showing that immunotherapy is more potent when given early in the day. Time to change our practice and give our IOs in the morning? At least until evidence of a circadian biology supporting the hypothesis & availability of data from phase III trials?

Impower 151 did not confirm the results of impower 150 in patients with EGFRmut NSCLC. On the primary outcome, PFS, no benefit of pemetrexed/pacli-carbo-beva-atezo over pemetrexed/pacli-carbo-beva. #WCLC2023

Flaura-2: escalation from osi to osi + CT makes sense in pts with ‘hard to treat’ EGFRmut NSCLC: exon 21, brain mets, and probably if symptoms/high tumor burden since PS1 pts derive more benefit than PS0. ~5X more Gr3 AEs & no signal in OS: not obvious in all comers. #WCLC2023

Part of the ⁦Gustave Roussy⁩ Thoracic Team and friends around our dear ⁦IASLC⁩ president ⁦Heather Wakelee⁩! #WCLC23

Adjuvant alectinib improves DFS vs chemotherapy in pts after resection of a stage IB to IIIA ALK+ NSCLC . Results of phase III trial ALINA spkl.io/60134l8TL. Impact on OS, rate of cross over and brain mets incidence to be followed. Likely to be a new SoC. ALK Positive