Result: Adding platinum–pemetrexed to osimertinib improved OS vs osimertinib alone.

Key data: mOS 47.5 vs 37.6 mo; HR 0.77 (95 % CI 0.61–0.96). Benefit consistent; manageable AEs.

Why it matters: Confirms OS gain; chemo-TKI becomes first-line standard for eligible EGFRm patients.

Result: Sacituzumab tirumotecan (ADC) improved PFS and OS vs chemo after EGFR-TKI failure.

Key data: PFS HR ≈ 0.50; interim OS trend favoring ADC; grade ≥3 TRAEs ≈ chemo; no ILD.

Why it matters: First TROP-2 ADC to surpass chemo; new post-TKI benchmark in EGFRm disease.

Result: Alectinib maintained durable OS and tolerability vs crizotinib in 1L ALK+ NSCLC.

Key data: mOS 81.1 vs 54.2 mo; sustained CNS control; no new toxicities.

Why it matters: Longest OS reported in advanced NSCLC; sets the bar for next-gen ALK strategies.

Result: Peri-operative pembrolizumab continued to improve both EFS and OS versus chemotherapy alone after 5 years of follow-up.

Key data: 5-y EFS 49.9 vs 26.5 %; HR 0.58; 5-y OS 64.6 vs 53.6 %; HR 0.74.

Why it matters: Confirms durable benefit; peri-op pembro now long-term standard in resectable NSCLC.

Result: Adjuvant ensartinib significantly prolonged DFS post-resection of ALK+ NSCLC.

Key data: DFS HR 0.20 (95 % CI 0.10–0.37); 2-y DFS 87 vs 57 %; CNS-DFS HR 0.22.

Why it matters: First ALK TKI with adjuvant DFS benefit; extends ADAURA model to ALK disease.

Result: Atezo + tira failed to improve PFS/OS vs durva after cCRT in stage III NSCLC.

Key data: PFS 14.2 vs 13.8 mo (HR 1.00); OS 45.6 vs 45.8 mo (HR 0.98).

Why it matters: Durvalumab remains SOC post-cCRT; TIGIT adds no incremental benefit here.

Result: Ivonescimab + chemo improved PFS vs tislelizumab + chemo in 1L Sq-NSCLC.

Key data: mPFS 11.1 vs 6.9 mo; HR 0.60 (95 % CI 0.46–0.78); PD-L1-independent.

Why it matters: First head-to-head bispecific vs PD-1 backbone; potential new 1L option pending OS readout.

Result: Adding LCT to osimertinib extended disease control in EGFR-mut metastatic NSCLC.

Key data: mPFS 25.4 vs 17.0 mo; HR 0.60 (p = 0.02); no new toxicities.

Why it matters: Supports multimodal approach for oligometastatic and/or oligoprogressive EGFR disease.

Result: Both TKIs showed high response rates and durable activity.

Key data: (Zongertinib) ORR 77 %, 6-mo PFS 79 %; (Sevabertinib) ORR 64 % pretreated, 71 % naïve; median PFS 8–11 mo; AEs mainly GI, no ILD.

Why it matters: Signals transition from ADC-based to oral HER2-targeted sequencing.

ICI de-escalation: Dose/frequency may be over-engineered upward; pharmacology suggests room for less intense maintenance; RCTs ongoing.

Sequencing logic: ADCs moving earlier; bispecifics testing PD-1 backbones; LCT integration in EGFR oligomet disease.

ALK vs EGFR reality: ALK survival approaches double EGFR; CNS control is crucial for long-term outcomes.

ctDNA, MRD & AI: ctDNA-MRD guides peri-op risk assessment months before radiologic relapse; AI-driven radiomics and pathology tools in early validation for response prediction.