Study: Phase 1b trial testing DLL3 bispecific T-cell engager tarlatamab combined with PD-L1 inhibitor as maintenance therapy after chemo-IO in extensive-stage SCLC.

Key data: In phase 1b (n=88), maintenance tarlatamab + atezolizumab/durvalumab after chemo-IO showed median OS 25.3 mo (95% CI 20.3–NE), with 12/18-mo OS 82%/75%. Median PFS 5.6 mo; ORR 24%; CRS mostly grade 1–2 (56%).

Why it matters: First prospective signal that DLL3 bispecific engagement + PD-L1 may dramatically extend survival in ES-SCLC. A potential paradigm shift if phase III confirms.

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Study: Systematic review/meta-analysis of 20 studies (n=5027) comparing outcomes of stopping ICIs at 2 years versus continuing beyond 2 years in advanced NSCLC.

Key data: Meta-analysis of 20 studies (n=5027) showed no OS difference between stopping ICIs at 2 years vs continuing indefinitely (5-yr OS ~69–83% both). Continuous therapy led to more cumulative irAEs. Re-challenge effective in relapsed patients.

Why it matters: Supports elective discontinuation at 2 years as safe, cost-effective, and less toxic for long-term responders.

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Study: Randomized phase II trial of consolidative nivolumab vs observation after neoadjuvant chemo-immunotherapy and chemoradiation in unresectable stage III NSCLC.

Key data: In this phase II RCT (n=172), consolidative nivolumab improved PFS vs observation (NR vs 12.2 mo; HR 0.49, p=0.003). Trend to OS benefit (18-mo OS 73% vs 61%). Grade ≥3 AEs 9%; one TRD (pneumonitis). High TMB associated with greater benefit.

Why it matters: Extends the PACIFIC principle into modern induction chemo-IO + cCRT settings.

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Study: Retrospective Chinese registry comparing five treatment strategies in unresectable stage III NSCLC: standard CRT→IO (PACIFIC), IO integrated with CRT or chemo, and non-IO controls.

Key data: Median PFS 25.8 mo with standard CRT→IO, 21.7 mo with IO+CRT→IO, 16.8 mo with IO+Chemo→IO, 14.8 mo with CRT alone, 7.1 mo with chemo alone. OS ~50–58 mo in IO arms. Grade ≥3 pneumonitis 8.5% with CRT→IO.

Why it matters: Validates PACIFIC outcomes in real-world practice and shows early IO+CRT integration is feasible and comparably effective, offering flexibility in sequencing.

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Study: Global registry + AI analysis of long-term outcomes in advanced NSCLC patients treated with first-line pembrolizumab monotherapy (PD-L1 ≥50%).

Key data: Median OS 21.8 mo; 5-yr OS 27%. Early mortality linked to ECOG ≥2, steroids, bone mets; long-term survival shaped by host factors (BMI, dyslipidemia, CV health).

Why it matters: 1 in 3 patients alive at 5 years. Survivorship care and host comorbidities are crucial; AI prognostics may refine risk stratification.

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Study: Meta-analysis pooling data on neoadjuvant chemo-immunotherapy in stage III NSCLC, focusing on pathological and surgical outcomes.

Key data: Pooled pCR 38%, MPR 65%, downstaging 77%, resection 88% (R0 99%). SAEs 13%.

Why it matters: Strong pathological responses and surgical feasibility, but heterogeneous data; survival impact still maturing.

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Study: Meta-analysis of 25 RCTs and cohort studies testing whether metformin enhances radiotherapy outcomes across cancer types.

Key data: No consistent survival benefit across tumor types; safety acceptable. Breast RT subgroup: lower cardiac events.

Why it matters: Refutes routine metformin as a radiosensitizer; possible niche cardioprotective role.

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Study: Phase II trial + biomarker analysis of poziotinib in EGFR exon20 insertion NSCLC, stratifying near-loop vs far-loop insertions.

Key data: ORR 14.8%, median PFS 4.2 mo. Near-loop insertions more responsive than far-loop (PFS 5.5 vs 3.5 mo). High grade ≥3 AEs (61%).

Why it matters: Biology of insertion site matters for TKI response. Not practice-changing but guides drug development and selection.

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Study: Meta-analysis of POU2F3 expression as a biomarker in SCLC and NECs.

Key data: POU2F3+ SCLC associated with improved OS (HR 0.74) and PFS (HR 0.69). Effect not seen in chemo-IO cohorts.

Why it matters: Confirms SCLC tuft-cell subtype as prognostic; predictive value for therapy remains uncertain.

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Study: Meta-analysis of dual PD-(L)1 + CTLA-4 blockade in mesothelioma across real-world and trial datasets.

Key data: Median OS 15.2 mo; PFS 5.8 mo; ORR 27%; grade ≥3 TRAEs 28%.

Why it matters: Reinforces CheckMate-743 findings; real-world and meta-analytic confirmation, but not novel.

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Study: National registry benchmarking durvalumab outcomes after CRT in stage III NSCLC vs PACIFIC trial.

Key data: Median OS 50 mo (PACIFIC: 48); 2-yr OS 68% vs 66%. Better outcomes in non-squamous (57 mo) and females (NR).

Why it matters: Confirms PACIFIC outcomes at national scale in a real-world NHS population, supporting broad adoption.

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