Rohit Singh, MD, FACP

PERSEE trial addresses a question I often discuss with patients: if PD-L1 is >50%, should we use pembrolizumab alone or add chemotherapy? In this randomized phase III trial, adding chemotherapy improved median PFS from 6.9 to 16.1 months (HR 0.56) and response rates from 50.3% to 77.5%. That is a substantial difference in disease control. The tradeoff was also substantial: grade ≥3 treatment-related toxicity increased from 19.3% to 53.8%. Median OS is numerically way longer, 50.2 vs 29.9 months, but the difference was not statistically significant (HR 0.77; 95% CI 0.57–1.05). We should be careful about how we describe that finding. These results would strengthen my preference for chemoimmunotherapy in a fit patient with symptomatic or rapidly progressing disease, where an early response matters. I would still discuss pembrolizumab alone with selected patients. High PD-L1 expression is useful, but the treatment decision also needs to account for disease burden, symptoms, comorbidities and what the patient values. I’d particularly like to see the quality of life results, subsequent treatments and detailed subgroup analyses. This is a very important and relevant study that gives us better evidence for a very practical conversation. Decroisette et al. PERSEE, ESMO 2026, abstract 2614O. @LungSummit @lcrf_org @myESMO @UVMLarnerMed @UVMcancercenter #ESMO26 #LCSM #NSCLC

Big update in extensive-stage SCLC. DeLLphi-305 showed that adding tarlatamab to durvalumab maintenance improved median OS from 12.7 to 21.1 months and PFS from 1.9 to 7.4 months, measured from maintenance randomization. These are impressive results, and I can see this changing our maintenance discussions with patients. I’m still thinking through two questions. First, where does this leave lurbinectedin + atezolizumab maintenance from IMforte? The DeLLphi-305 numbers look better, but we cannot establish superiority by comparing results across trials. Second, what do we give after progression on tarlatamab + durvalumab? Trials, platinum rechallenge in selected patients, and lurbinectedin/topotecan are considerations, but we need better evidence in patients whose disease has progressed on tarlatamab. Keeping tarlatamab for second line is an understandable argument. In clinic, though, we also see patients deteriorate too quickly to receive the next treatment. One detail I’d particularly want to examine is how many patients in the control arm received tarlatamab after progression. That matters when discussing early treatment versus reserving it for relapse. I’m encouraged by these results. Alongside working out the best sequence, we’ll need to make treatment accessible and have the staffing, monitoring and caregiver support to deliver it safely. https://t.co/IKFyOZ8ln6 #ESMO26 #LCSM #SCLC @UVMcancercenter @myESMO @lcfamerica @SclcSMASHERS

Big update in extensive-stage SCLC. DeLLphi-305 showed that adding tarlatamab to durvalumab maintenance improved median OS from 12.7 to 21.1 months and PFS from 1.9 to 7.4 months, measured from maintenance randomization. These are impressive results, and I can see this changing our maintenance discussions with patients. I’m still thinking through two questions. First, where does this leave lurbinectedin + atezolizumab maintenance from IMforte? The DeLLphi-305 numbers look better, but we cannot establish superiority by comparing results across trials. Second, what do we give after progression on tarlatamab + durvalumab? Trials, platinum rechallenge in selected patients, and lurbinectedin/topotecan are considerations, but we need better evidence in patients whose disease has progressed on tarlatamab. Keeping tarlatamab for second line is an understandable argument. In clinic, though, we also see patients deteriorate too quickly to receive the next treatment. One detail I’d particularly want to examine is how many patients in the control arm received tarlatamab after progression. That matters when discussing early treatment versus reserving it for relapse. I’m encouraged by these results. Alongside working out the best sequence, we’ll need to make treatment accessible and have the staffing, monitoring and caregiver support to deliver it safely. https://t.co/IKFyOZ8ln6 #ESMO26 #LCSM #SCLC @UVMcancercenter @myESMO @lcfamerica @SclcSMASHERS

Really interesting biomarker analysis from Tina Cascone and colleagues from CheckMate 77T in Nature. Perioperative nivolumab + chemo increased pre-surgical ctDNA clearance (66% vs 38%), and ctDNA clearance strongly tracked with pCR and EFS. The most striking finding for me: every patient who converted from post-op MRD-negative to MRD-positive ultimately recurred. PD-L1 still appears meaningful, with the strongest EFS signal in PD-L1 >50%, while benefit was still seen across PD-L1 groups. Squamous histology also had a numerically stronger EFS benefit than non-squamous disease. Field is moving toward dynamic, risk-adapted perioperative therapy using ctDNA clearance + pathologic response + post-op MRD rather than relying on static genomics alone. Not practice-changing yet for escalation/de-escalation, but definitely where the next generation of trials should go. @Lung_Cancers #lcsm #lungcancer https://t.co/wDCIK3Usfx

EGFR exon20ins NSCLC is finally entering the targeted-therapy era. In the phase III WU-KONG28 trial, first-line sunvozertinib outperformed platinum/pemetrexed: • mPFS: 10.3 vs 7.5 mo (HR 0.65) • ORR: 58.9% vs 31.1% • DoR: 11.2 vs 7.1 mo • 12-mo PFS: 46.1% vs 26.7% An https://t.co/HUj58RIptp

Great to see prospective intracranial activity with tarlatamab in SCLC brain mets. I’ve been using it in selected patients with asymptomatic CNS disease and, at times, deferring upfront radiation. Encouraging to finally see supporting data from DeLLphi-304. #SCLC #ASCO26 https://t.co/V3015i24k6