Benjamin Besse

KRAS inhibitors in NSCLC: -G12Di: coming soon to meet a major unmet need — same activity in smokers vs never-smokers? -G12Ci: expanding field, active in both naïve and post-sotorasib/adagrasib pts. Excellent summary @GarridoLagunaMD #ESMO25

ALEX final OS: - crizo arm dragged down by <50% getting next-gen ALK. Lack of crossover really hurts. - 5-yr OS with alectinib ≈ 5-yr PFS with lorlatinib (CROWN), but only 18% got lorla post alect — we still don’t know the optimal sequence. #ESMO25

Is MET IHC predictive of amivantamab efficacy? Chrysalis-2 in EGFRmut NSCLC post-osimertinib (biopsy at resistance). Cohorts D&E: ami+lazertinib | Cohort F: ami monotherapy. ORR higher with MET+, but also seen in MET–. #WCLC25

Be ready to screen MTAP loss in all pts with advanced NSCLC, regardless of driver. @mihaela_aldea shows incidence, highest in ALK/RET/EGFR/ROS1. AMG193 paved the way at #ESMO24. BMS-986504 confirms druggability: 29% ORR + many durable SD (slide @CharuAggarwalMD). #WCLC25

EGFR update 7 potential options: •3rd gen TKI: osimertinib, lazertinib, aumolertinib •Amivantamab •Pemetrexed •Carboplatin •Ivonescimab •Dato-DXd OS data favor combos upfront—but real-world ≠ trial. In RWD, ~40% of newly diagnosed pts wouldn’t qualify for FLAURA2 #WCLC25

Up to 50% of patients with metastatic cancer develop lung metastases, linked to poor prognosis and impaired quality of life. Our Nature Reviews Disease Primers article unpacks biology, diagnosis & treatment strategies. @LodovicaZullo @GustaveRoussy nature.com/articles/s4157…

@n8pennell @DrJNaidoo In our own dataset (Rousseau et al., EJC 2023), the effect of C1D1 timing was striking. All studies should also consider analyzing this specific time point.

@DrJNaidoo @BenjaminBesseMD It would almost have to be the first administration that mattered most, and then if the immune system was not ready at exactly that time it somehow closed the window for response later on. It doesn’t seem impossible just implausible.

Maybe this is a dumb question but aren’t the long half life antibodies still there the next morning?

@HosseinBorghaei @StephenVLiu My main question concerns the long half-life of IO: perhaps the timing of the first dose (D1C1) is what truly matters, since IO concentrations remain high even at three weeks, making subsequent dosing less sensitive to timing.

@BenjaminBesseMD @StephenVLiu This is fascinating. Are there other cofounders?

Morning > Afternoon for IO? Evidence is mounting—retrospective and now prospective (210 pts, randomized, PFS HR 0.42 but no PD-L1 strat). Given IO’s long half-life, maybe only the timing of the first dose matters. #ASCO2025

@HosseinBorghaei @StephenVLiu The trial included no stratification factors—notably, PD-L1—and patient characteristics were not presented. A pity, in my view, as this study deserved selection as an oral presentation rather than a mini-oral, especially with a strong discussant.

@Amolpatel_dr @DrJNaidoo @myESMO @OncoAlert PULSE trial : recruitment ongoing in France, Spain and Belgium about to open, Greece and Estonia will follow!

@DrJNaidoo @BenjaminBesseMD @myESMO @OncoAlert Do you any access or information on interim analysis? Please share - if possible. I will be delivering a talk at AACR 2025. It is important to discuss such trials.

#ELCC25 De-escalation clinical trials in NSCLC Impassioned presentation of the key trials, that can save pt’s time, toxicity, & ensure healthcare system sustainability - PULSE 🇫🇷 - Osi-Save 🇳🇱 - REFINE-Lung 🇬🇧 @BenjaminBesseMD, best in the business @myESMO @OncoAlert #LCSM

Debate on L1 for EGFR mut NSCLC : ‘easy osi’ then escalate to CT-ami, or use doublet upfront? Lazertinib+amivantmab likely to extend OS by ~ 1 yr vs osimertinib, but without cross over to CT-ami. Intensify only if ctEGFR not cleared after 4w of osi? #ELCC25

ICB or chemo-ICB in PD-L1≥50% advanced NSCLC? Metabolic tumor volume (tMTV) assessed by 18F FDG petscan can guide you. High tMTV lesions might have a different biology and be better candidate to chemo-ICB. @FilippoDallOlio aacrjournals.org/clincancerres/…

NUT Carcinoma is an ultra-rare entity with a NUTM1 fusion, diagnosed by a simple IHC NUT+ (can look like a squamous lung cancer in a never smoker pt). Previously known as midline carcinoma, its prognosis is extremely poor. Lurbinectedin appears promising! annalsofoncology.org/article/S0923-…

YES! De-escalation trials matter and should be much more supported by payers! Very preliminary results from the Dutch non inferiority trial DEDICATION-1 are reassuring. In France, the PULSE trial has the same hypothesis, opens soon in Belgium, Spain, Estonia and Greece! #ESMO24

Impressive benefit for Lenvatinib-Pembrolizumab in pts with thymic carcinoma and B3 thymoma. ORR 23.3% and mPFS 14.9m are unexpected in 2nd line or more. Lenvatinib dose matters in a subgroup analysis. Congratulations @JordiRemon #ESMO24

Adjuvant Durvalumab after resection of stage IB~IIIA NSCLC does not improve DFS. No predictive effect of PD-L1 expression as in KN-091/PEARLS (adj pembro): Biology of micrometastatic disease differs from matched primary tumor? Confirms that neoadjuvant is the way to go. #ESMO24

1st phase III trial of an ADC vs docetaxel in a biomarker selected population Tusamitamab Ravtansine targets CEACAM5, overexpressed in 25% of non sq NSCLC CARMEN LC03 did not meet the primary endpoints PFS and OS. #WCLC24

Stop pembro after 2 years? In 43,359 pts that received up-front pembrolizumab for an advanced NSCLC, continuation beyond 2 years was not associated with better OS than a fixed 2-year treatment, HR = 0.97 [0.75–1.26] p = 0.95. @arousseaumd sciencedirect.com/science/articl…

@GustaveRoussy @ASCO #ASCO24 140 accepted abstracts, #30 oral presentations w #10 done by our experts. We’re here to exchange, collaborate and drive the next steps on the road to cure cancer. @AlbigesL