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Lung adenocarcinoma — statistics and effect-size ledger¶
Purpose and interpretation rules¶
This sheet preserves reusable denominators, effect sizes, confidence intervals, dates, populations, and methods. It is not a treatment algorithm. Unless a row explicitly says adenocarcinoma, the estimate applies to broader lung cancer or NSCLC and must not be silently relabelled.
- HR/RR below 1 favors the first-listed intervention for the adverse endpoint stated.
- Medians cannot be subtracted to estimate an individual's survival gain.
- Single-arm response rates do not rank therapies across trials.
- DFS, EFS, PFS, OS, pCR, ORR, and patient-reported outcomes are not interchangeable.
- Modelled burden, registry incidence, and trial efficacy answer different questions.
- Earlier rows retain their dated verification history. The 2026-10-23 addition was checked through live PubMed E-utilities and Crossref; its numerical claims below were read on the cited government portals, not inferred from a journal abstract. 2026-10-30 trial rows were taken from PubMed abstracts in this session; full texts were not opened.
Global burden and population trends¶
| Domain | Population/method | Estimate | Boundary | Source |
|---|---|---|---|---|
| Global lung-cancer burden, 2022 | GLOBOCAN model, 185 countries | Lung cancer was the most commonly diagnosed cancer and leading cancer-death cause | Not histology-specific | PMID 38572751 |
| Adenocarcinoma distribution, 2022 | GLOBOCAN/CI5/AFCRN reconstruction | Leading lung-cancer subtype in most assessed countries | Modelled subtype estimates | PMID 39914442 |
| Japan localized adenocarcinoma trend | 62,870 cases, 1993–2015 | Annual change +4.5% men; +5.7% women | Detection/classification contribute | PMID 35138642 |
| Metastatic lung-cancer 1-y survival | California registry, 186,156 cases, 1990–2014 | 18.4% → 29.4% | All histologies | PMID 33414054 |
| US NSCLC mortality | SEER incidence-linked mortality, men, 2013–2016 | Mortality −6.3%/y; incidence −3.1%/y | Temporal attribution, not randomized | PMID 32786189 |
| US 2-y lung-cancer-specific survival | Diagnoses 2001 vs 2014 | 26% → 35% | All NSCLC mix | PMID 32786189 |
| Deaths averted 1975–2020 | US national modelling | Tobacco control dominant; screening/treatment add later gains | Model-dependent decomposition | PMID 39636625 |
| US Hispanic/Latino cancer statistics, 2026 | ACS; federal registry and vital-statistics data | Hispanic people have about half the lung-cancer incidence of White people; male incidence fell partly through declining lung cancer | All histologies; continental US + Hawaii | PMID 42831778 |
| Adolescent and young-adult lung cancer, 2022 | GLOBOCAN 2022 (185 countries) + CI5 trends 2003–2017, ages 15–39 | 31,681 cases, 15,189 deaths; Asia 78.3% of cases; adenocarcinoma incidence rose significantly in several countries (both sexes in China, Korea, UK) | Modelled; small numbers by country | PMID 42873587 |
US surveillance update checked 2026-10-23¶
| Domain | Population/method and period | Estimate | Boundary | Source |
|---|---|---|---|---|
| Lung-cancer mortality trend | US vital statistics; percentage change in rates, 2004–2023 | −52% in males; −37% in females | All lung-cancer histologies; population trend, not a treatment effect | (CDC — "Annual Report to the Nation on the Status of Cancer", https://www.cdc.gov/cancer/research/arn.html, accessed 2026-10-23) |
| Up-to-date lung-cancer screening | Eligible US adults, 2024; reported screening uptake | 18.7% | Broad lung-cancer screening; eligibility and survey method matter; not an adenocarcinoma-specific estimate | (NCI/SEER — "Annual Report to the Nation 2026: 21st Century Progress Against Lung Cancer", https://seer.cancer.gov/report_to_nation/lung.html, accessed 2026-10-23) |
The associated journal report is Henley et al. (2026, PMID 42770880). Its metadata and retraction status were checked in PubMed and Crossref; journal full text was not retrieved. The two rows use the open government pages directly. The portals use different historical screening baselines, so no pooled baseline-to-2024 change is calculated.
Tobacco, never-smoking, pollution, and susceptibility¶
| Exposure/population | Estimate | Method/caution | Source |
|---|---|---|---|
| Biochemically confirmed active smoking in women | RR 7.8 vs non-smokers | Prospective cohort; historical exposure | PMID 7669596 |
| Spousal second-hand smoke | RR 1.24 (95% CI 1.13–1.36) | 37-study meta-analysis; 4,626 never-smoker cases | PMID 9365295 |
| Spousal second-hand smoke, later synthesis | RR 1.25 (1.15–1.37) | 51 studies, 7,369 cases | PMID 12058801 |
| Workplace second-hand smoke | RR 1.17 (1.04–1.32) | Observational synthesis | PMID 12058801 |
| Japanese never-smoking women | 109 lung cancers/28,414 over 13 y; 82 adenocarcinomas | Prospective cohort; exposure-dependent spousal association | PMID 17935128 |
| COPD | SRR 2.06 (1.50–2.85) | Prospective-cohort meta-analysis; shared smoking confounding | PMID 29100446 |
| Emphysema | SRR 2.33 (1.56–3.49) | Same synthesis | PMID 29100446 |
| Asian advanced adenocarcinoma EGFR prevalence | 51.4% of 1,450 evaluable tumors | PIONEER; advanced Asian cohort, not global | PMID 24419411 |
| Never-smoker geographic KRAS variation | 3.8× more frequent in North America/Europe than East Asia | 871 tumors, 28 locations; research cohort | PMID 40604281 |
| Air-pollution mechanistic cohort set | 32,957 EGFR-driven cases across four within-country cohorts | PM2.5 association plus mouse/organoid IL-1β experiments | PMID 37020004 |
| Never-smoker TALENT screening | High early-stage detection in risk-enriched cohort | Single arm; no mortality or overdiagnosis comparator | PMID 38042167 |
| PM2.5 constituents in never-smokers | Nitrate HR 1.35, ammonium 1.22, chloride 1.20 per IQR; mixture HR 1.13 | China Kadoorie Biobank, 262,785 never-smokers, 2,646 cases; histology not given in abstract | PMID 42828982 |
| Wildfire vs non-wildfire PM2.5 and survival after diagnosis | All-cause death HR 1.078 vs 1.017 per 1 µg/m³ | SEER-Medicare, 414,016 patients ≥65; survival, not incidence | PMID 42743939 |
| Germline EGFR T790M | Associated with lung-cancer risk in >3.3 million individuals; risk several-fold higher in never-smokers | Abstract gives no effect estimate; founder-population enrichment | PMID 42752144 |
Screening efficacy and harms¶
| Study/policy | Population | Benefit | Harm/implementation | Source |
|---|---|---|---|---|
| NLST | 53,454 high-risk participants | Lung-cancer mortality −20.0% (95% CI 6.8–26.7); all-cause −6.7% | Trial positivity generated many false positives | PMID 21714641 |
| NLST initial round | LDCT arm | Positive screen 27.3%; cancer in 3.8% of positive screens | Older low positivity threshold | PMID 23697514 |
| NELSON men | 13,195 men | 10-y lung-cancer mortality rate ratio 0.76 (0.61–0.94) | Volumetry/doubling-time protocol | PMID 31995683 |
| NELSON women | 2,594 women | Smaller subgroup; favorable mortality direction | Underpowered sex-specific estimate | PMID 31995683 |
| USPSTF 2021 eligibility | US adults | Annual LDCT age 50–80, ≥20 pack-years, current or quit ≤15 y | Policy threshold, not biologic boundary | PMID 33687470 |
| Risk-model selection | US modelling | More cost-effective at selected thresholds than categorical rules | Assumptions drive result | PMID 36745885 |
| Never-smoker screening | TALENT ages 55–75 with added risks | Substantial detection, enriched by family history | No randomization; cannot infer mortality benefit | PMID 38042167 |
| BioMILD ~10-y follow-up | 4,119 heavy smokers; triennial LDCT after negative baseline | LC incidence 3.0% (baseline-negative) vs 21.8% (baseline-positive); stage I about half or more in all intervals | Adherence 92% at 3–5 y, 58% beyond 9 y; no unscreened control | PMID 42777510 |
| CPH-Lung blood-informed risk model | Copenhagen cohorts, ever-smokers ≥50 | 6-y AUC 0.783 vs 0.720 (PLCOm2012); sensitivity in women 57.6% vs 39.2% at matched specificity | Single country; discrimination only | PMID 42863103 |
| Cessation in underserved screening referrals | 3,220 randomized current smokers | 6-mo verified abstinence 4.3% (usual care), 5.1% (+ free pharmacotherapy), 8.8% (+ incentives), 7.2% (+ incentives + mHealth) | Absolute quit rates low | PMID 42832220 |
Histology, grade, and staging¶
| Domain | Denominator/result | Interpretation | Source |
|---|---|---|---|
| TCGA adenocarcinoma | 230 resected tumors | Mean 8.9 somatic mutations/Mb; 18 significantly mutated genes | Resection cohort, bulk multi-omics |
| AIS/MIA outcome | Resected cohorts | Near-100% disease-specific survival after complete resection | Requires complete sampling/classification |
| STAS staging evaluation | 4,061 pathologic stage-I NSCLCs | Prognostic descriptor proposed, not T-category determinant | Retrospective international analysis |
| TNM-9 source database | 124,581 registrations | 76,518 informed stage-group analysis | International registry; exclusions apply |
| TNM-9 clinical-stage analysis | 58,193 cases | Used in stage-group proposal | Histology mixed |
| TNM-9 pathologic-stage analysis | 39,192 cases | Used in stage-group proposal | Operated selection |
| TNM-9 best-stage analysis | 62,611 cases | Used in stage-group proposal | Mixed clinical/pathologic information |
| TNM-9 metastatic analysis | 14,937 stage IVA–IVB NSCLCs | Supported M1c single- versus multiple-organ subdivision | Prognostic, not treatment selector |
Surgery and local consolidation¶
| Trial/setting | Comparison | Estimate | Boundary | Source |
|---|---|---|---|---|
| JCOG0802/WJOG4607L | Segmentectomy vs lobectomy, peripheral ≤2 cm | OS criterion favored segmentectomy; more local relapse | Selected Japanese peripheral tumors | PMID 35461558 |
| CALGB 140503 | Sublobar vs lobar, peripheral cT1aN0 ≤2 cm | DFS noninferior; OS similar | Intraoperative node-negative confirmation | PMID 36780674 |
| Gomez oligometastatic phase II | Local consolidation vs maintenance/observation | PFS 14.2 vs 4.4 mo; OS 41.2 vs 17.0 mo | 49 selected patients; older systemic era | PMID 31067138 |
| Iyengar phase II | SABR + maintenance vs maintenance | PFS 9.7 vs 3.5 mo | Small trial stopped early for efficacy | PMID 28973074 |
| SABR-COMET | SABR vs standard care, mixed cancers | Long-term OS benefit | NSCLC subset small | PMID 32484754 |
Adjuvant and perioperative therapy¶
| Trial/analysis | Comparison | Effect size | Key boundary | Source |
|---|---|---|---|---|
| LACE | Cisplatin chemotherapy vs none; 4,584 resected NSCLCs | OS HR 0.89 (0.82–0.96); 5-y absolute benefit 5.4% | Historical, mixed histology | PMID 18506026 |
| LACE stage IA | Same | OS HR 1.40 | No demonstrated benefit | PMID 18506026 |
| LACE stage IB | Same | OS HR 0.93 | Modest/uncertain | PMID 18506026 |
| LACE stage II | Same | OS HR 0.83 | Benefit-concentrated subgroup | PMID 18506026 |
| LACE stage III | Same | OS HR 0.83 | Benefit-concentrated subgroup | PMID 18506026 |
| ADAURA stage II–IIIA | Osimertinib vs placebo | DFS HR 0.17 | EGFR exon19del/L858R; optional chemotherapy | PMID 32955177 |
| ADAURA stage IB–IIIA | Osimertinib vs placebo | DFS HR 0.20 | Three-year planned therapy | PMID 32955177 |
| ADAURA OS | Osimertinib vs placebo | Death HR 0.49; 5-y OS 88% vs 78% | Salvage patterns evolve | PMID 37272535 |
| ADAURA 8-y landmark | Same, post hoc | Stage IB–IIIA OS HR 0.52; 8-y OS 79% vs 64%; stage II–IIIA HR 0.53, 74% vs 58% | 127 of 558 patients alive at the earlier cutoff not followed further | PMID 42732874 |
| ICWIP | 3-y icotinib vs placebo after adjuvant chemotherapy (n=135) | DFS HR 0.54; OS HR 0.84 (0.39–1.81) | Small; recruited 2014–2018 | PMID 42660909 |
| LAURA | Osimertinib vs placebo after chemoradiation, unresectable stage III EGFR (n=216) | PFS 39.1 vs 5.6 mo; HR 0.16 | Crossover at progression | PMID 38828946 |
| LAURA interim OS 2 | Same | OS HR 0.67 (0.40–1.14), 31% maturity; PFS2 HR 0.62 | Open-label osimertinib after placebo progression | PMID 42714840 |
| S1914 | SABR ± atezolizumab, inoperable early-stage (n=402 eligible) | OS HR 1.04 (0.69–1.58); 2-y OS 82% both arms | Grade ≥3 AE 12% vs 3%; closed for futility | PMID 42702214 |
| KEYNOTE-867 | SBRT ± pembrolizumab, unresected stage I–II (n=448) | EFS 31.2 vs 28.3 mo, HR 0.92 (0.69–1.24) | Stopped early; grade 3–5 TRAE 20.4% vs 3.7%; 5 treatment-related deaths, all pembrolizumab | PMID 42950173 |
| R-ALPS | Benmelstobart ± anlotinib vs placebo after CRT, China (n=553) | Stage-1 PFS 15.1 / 9.7 / 4.2 mo; HRs 0.49 and 0.53 vs placebo | Anlotinib add-on vs benmelstobart HR 0.82 (0.63–1.08); grade 5 TRAE 7.2% vs 1.4% vs 1.5%; 89.5% male | PMID 42955021 |
| CheckMate 816 | Nivolumab-chemo vs chemo | EFS 31.6 vs 20.8 mo; HR 0.63 (97.38% CI 0.43–0.91) | Mixed NSCLC, driver caveats | PMID 35403841 |
| CheckMate 816 pCR | Same | 24.0% vs 2.2% | pCR prognostic, not individual switch rule | PMID 35403841 |
| CheckMate 816 surgery | Same | Surgery 83.2% vs 75.4% | Protocol-selected resectable population | PMID 35403841 |
| CheckMate 816 grade 3–4 AE | Same | 33.5% vs 36.9% | Treatment-related | PMID 35403841 |
| KEYNOTE-671 | Perioperative pembrolizumab vs placebo | 24-mo EFS 62.4% vs 40.6%; HR 0.58 | Cannot isolate adjuvant component | PMID 37272513 |
| KEYNOTE-671 pCR | Same | 18.1% vs 4.0% | Mixed histology | PMID 37272513 |
| KEYNOTE-671 grade ≥3 AE | Same | 44.9% vs 37.3% | Treatment-related | PMID 37272513 |
| AEGEAN | Perioperative durvalumab vs placebo | EFS HR 0.68 (0.53–0.88); pCR 17.2% vs 4.3% | EGFR/ALK excluded from efficacy analysis | PMID 37870974 |
| AEGEAN grade 3–4 AE | Same | 42.4% vs 43.2% | Treatment-related | PMID 37870974 |
| AEGEAN update | Same; second interim EFS, interim OS | EFS HR 0.69 (0.55–0.88); OS HR 0.89 (0.70–1.14); DFS HR 0.66 | Median follow-up 25.9 mo | PMID 42664473 |
| IMpower010 | Atezolizumab vs supportive care after chemotherapy | DFS HR 0.66 in stage II–IIIA PD-L1 ≥1% | Hierarchical analysis | PMID 34555333 |
| KEYNOTE-091 | Pembrolizumab vs placebo | DFS HR 0.76 overall; PD-L1 ≥50% HR 0.82, not significant at interim | PD-L1 pattern differs from metastatic setting | PMID 36108662 |
| PACIFIC five-year | Durvalumab vs placebo after chemoradiation | OS 42.9% vs 33.4%; PFS 33.1% vs 19.0% | Unresectable stage III, mixed histology | PMID 35108059 |
EGFR-targeted therapy¶
| Trial | Comparison/population | Efficacy | Safety/interpretation | Source |
|---|---|---|---|---|
| IPASS mutation-positive | Gefitinib vs carboplatin-paclitaxel | PFS HR 0.48 | Predictive interaction | PMID 19692680 |
| IPASS mutation-negative | Same | Gefitinib HR 2.85, favoring chemotherapy | Clinical phenotype cannot replace genotype | PMID 19692680 |
| FLAURA | Osimertinib vs gefitinib/erlotinib | PFS 18.9 vs 10.2 mo; HR 0.46 | Classical EGFR mutations | PMID 29151359 |
| FLAURA OS | Same | OS 38.6 vs 31.8 mo; HR 0.80 | Crossover/subsequent therapy matter | PMID 31751012 |
| FLAURA2 | Osimertinib + platinum-pemetrexed vs osimertinib | PFS 25.5 vs 16.7 mo; HR 0.62 | Added chemotherapy burden | PMID 37937763 |
| MARIPOSA | Amivantamab-lazertinib vs osimertinib | PFS 23.7 vs 16.6 mo; HR 0.70 | Infusion, rash, edema, VTE | PMID 38924756 |
| FLAURA2 final OS | Osimertinib + platinum-pemetrexed vs osimertinib (n=557) | OS 47.5 vs 37.6 mo; HR 0.77 (0.61–0.96) | Grade ≥3 AE 70% vs 34% | PMID 41104938 |
| MARIPOSA final OS | Amivantamab-lazertinib vs osimertinib (429 per arm) | OS HR 0.75 (0.61–0.92); 3-y OS 60% vs 51% | Grade ≥3 AE 80% vs 52% | PMID 40923797 |
| EGFR/TP53 co-mutant phase 3 (China) | Osimertinib + chemotherapy vs osimertinib (n=294) | PFS 34.0 vs 15.6 mo; HR 0.44 | OS 30.6% mature; TP53-wild-type not randomized | PMID 42574006 |
| HARMONi | Ivonescimab + chemo vs placebo + chemo after third-generation TKI (n=438) | PFS 6.8 vs 4.4 mo, HR 0.52; OS 16.8 vs 14.0 mo, HR 0.79 (0.62–1.01) | Correction notice published (PMID 42805208) | PMID 42636833 |
| HARMONi-A | Ivonescimab + chemo vs placebo + chemo after EGFR TKI, China (n=322) | OS 16.8 vs 14.1 mo, HR 0.74 (0.58–0.95); 30-mo OS 29.1% vs 18.4% | China-only; OS is key secondary after PFS; grade ≥3 TEAEs 67.1% vs 54.7% | PMID 42307937 |
| PANKU-Lung01 | Iza-bren vs platinum-pemetrexed after third-generation EGFR TKI, China (n=422 treated) | PFS 11.1 vs 5.7 mo, HR 0.40 | Grade ≥3 TRAEs 79% vs 62%; ILD 1% vs 0%; OS interim numbers not in the abstract | PMID 42933461 |
| HERON-Lung01 | Ruzaltatug rezetecan vs platinum-pemetrexed after EGFR TKI, China (n=498) | Interim PFS 8.3 vs 5.4 mo, HR 0.47 | Median follow-up 7.7 mo; grade ≥3 TRAEs 41% vs 39% | PMID 42933457 |
| Dalmelitinib + aumolertinib | EGFR-mutant MET-amplified after EGFR-TKI vs platinum chemo (n=314) | PFS 6.2 vs 4.4 mo, HR 0.60; ORR 59.6% vs 38.6% | OS immature; China; FISH MET copy ≥5 or MET/CEP7 ≥2 | PMID 42928710 |
| Oligometastatic LAT meta-analysis | 16 RCTs, 1,343 patients | PFS HR 0.63; OS HR 0.68; EGFR-mutant OS HR 0.52 | Abstract-sourced; more grade ≥3 AEs and pneumonitis | PMID 42955614 |
| STARLET (OUTRUN + LUOSICNS) | Upfront SRS + osimertinib vs osimertinib, brain metastases (n=79) | 12-mo intracranial PFS difference 11% (95% CI −10% to 32%), p=0.31 | Randomized phase 2 pooled analysis | PMID 41534788 |
| AURA3 | Osimertinib vs platinum-pemetrexed in T790M | PFS 10.1 vs 4.4 mo; HR 0.30 | Post-earlier-generation setting | PMID 27959700 |
| PAPILLON | Amivantamab-chemo vs chemo, EGFR exon20ins | PFS 11.4 vs 6.7 mo; HR 0.40 | First-line exon-20 insertion | PMID 37870976 |
Fusion-driver therapy¶
| Driver/trial | Population | Estimate | Boundary | Source |
|---|---|---|---|---|
| ROS1 crizotinib | Advanced ROS1-positive NSCLC | ORR 72%; median PFS 19.2 mo | Single-arm expansion | PMID 25264305 |
| RET selpercatinib | RET-fusion NSCLC | High response including CNS activity | Single-arm foundational cohorts | PMID 32846060 |
| LIBRETTO-431 | Selpercatinib vs platinum-pemetrexed ± pembrolizumab | Median PFS 24.8 vs 11.2 mo | Interim efficacy population | PMID 37870973 |
| NTRK larotrectinib | TRK-fusion cancers | High pooled response | Tissue-agnostic; small lung subset | PMID 29466156 |
| ALINA | Alectinib vs platinum chemotherapy after resection | Large DFS/CNS benefit | Mature OS and chemo additivity unresolved | PMID 38598794 |
| ELEVATE | Ensartinib vs placebo after adjuvant chemo, resected IB–IIIB ALK+ (n=274) | 24-mo DFS 86.4% vs 53.5% in II–IIIB; HR 0.20 | After chemotherapy; OS immature; grade ≥3 AE 35.8% vs 18.2% | PMID 42418775 |
| CROWN 7-year update | Lorlatinib vs crizotinib, untreated ALK+ (n=296) | 7-y PFS 55% vs 3%; HR 0.19; time to intracranial progression HR 0.06 | Post hoc; OS events not reached | PMID 42217582 |
| Envonalkib phase 3 (China) | Envonalkib vs crizotinib (n=264) | PFS 30.4 vs 12.0 mo; HR 0.48 | Crizotinib comparator; OS immature | PMID 42830869 |
KRAS, BRAF, MET, and HER2 therapy¶
| Trial | Population | Efficacy | Major caution | Source |
|---|---|---|---|---|
| CodeBreaK 100 | Previously treated KRAS G12C NSCLC | ORR 37.1%; median PFS 6.8 mo | Single arm | PMID 34096690 |
| CodeBreaK 200 | Sotorasib vs docetaxel | PFS HR 0.66; 5.6 vs 4.5 mo | No demonstrated OS advantage; crossover | PMID 36764316 |
| KRYSTAL-1 | Adagrasib, previously treated G12C | ORR 42.9%; median PFS 6.5 mo | Single arm | PMID 35658005 |
| MET capmatinib | METex14 cohorts | Higher ORR untreated than pretreated | Single-arm; edema | PMID 32877583 |
| MET tepotinib | METex14 cohorts | Clinically meaningful response | Single-arm; assay and edema | PMID 32469185 |
| DESTINY-Lung01 | T-DXd, HER2-mutant NSCLC | ORR 55%; duration 9.3 mo; PFS 8.2 mo | ILD 26%, including deaths | PMID 34534430 |
| DESTINY-Lung02 | T-DXd 5.4 vs 6.4 mg/kg cohorts | Activity preserved at lower dose | Lower dose favored benefit-risk | PMID 37694347 |
| Daraxonrasib phase 1–2 | Previously treated RAS-mutant NSCLC (n=136, ≤300 mg) | ORR 31%–37% by dose band | Grade ≥3 AE 54%; 4 grade 5 events; single arm | PMID 42685317 |
| Ifebemtinib + garsorasib | Untreated KRAS G12C NSCLC (n=33) | Confirmed ORR 82% | Single arm, China, 94% male | PMID 42413526 |
| Krascendo 1 | Divarasib vs sotorasib or adagrasib, previously treated G12C (n=338) | PFS 9.8 vs 5.7 mo, HR 0.58; OS 17.7 vs 12.0 mo, HR 0.56; ORR 58.4% vs 32.3% | Open-label; 156/171 controls received sotorasib; grade 3–4 TRAE 24.6% vs 34.5% | PMID 42929675 |
Driver-negative immunotherapy¶
| Trial | Comparison | Estimate | Boundary | Source |
|---|---|---|---|---|
| KEYNOTE-024 | Pembrolizumab vs chemo, TPS ≥50% | PFS 10.3 vs 6.0 mo; HR 0.50; ORR 44.8% vs 27.8% | EGFR/ALK-negative selected group | PMID 27718847 |
| KEYNOTE-189 | Pembrolizumab-platinum-pemetrexed vs chemotherapy | Initial OS HR 0.49; PFS HR 0.52 | Metastatic nonsquamous, EGFR/ALK-negative | PMID 29658856 |
| IMpower150 | Atezolizumab-bevacizumab-carboplatin-paclitaxel vs bevacizumab-chemo | OS/PFS benefit | Four-drug burden; mixed biomarkers | PMID 29863955 |
| PD-L1-negative pooled 5-y | Pembrolizumab-chemo vs chemo | OS HR 0.64 (0.51–0.79); PFS HR 0.66 (0.54–0.81); 5-y OS 12.5% vs 9.3% | Squamous+nonsquamous pooled | PMID 38642841 |
| EGFR-mutant PD-L1-positive pilot | Pembrolizumab, TKI-naive | No objective responses among eligible EGFR-mutant patients | Small phase II; stopped for futility | PMID 29874546 |
| PERSEE | Pembrolizumab + chemo vs pembrolizumab, PD-L1 ≥50% (n=321) | PFS 16.1 vs 6.9 mo, HR 0.56; OS 50.2 vs 29.9 mo, HR 0.77 (0.56–1.05) | Mixed histology; grade ≥3 TRAEs 54% vs 19%; OS not significant | PMID 42927854 |
ctDNA, MRD, and implementation¶
| Setting | Denominator/result | Meaning | Source |
|---|---|---|---|
| Localized lung-cancer MRD | Post-treatment ctDNA anticipated radiographic recurrence in some patients | Strong prognosis; action utility unproven | PMID 28899864 |
| TRACERx phylogenetic ctDNA | Personalized subclonal tracking | Reveals relapse evolution; low-shedding limitation | PMID 28445469 |
| LUNGCA-1 | Prospective multicentre postoperative cohort | ctDNA positivity associated with recurrence | Not randomized intervention |
| Newly diagnosed metastatic plasma NGS | Prospective complementary testing | Added actionable detections to tissue | Negative plasma non-exclusionary |
| Reflex testing | Program implementation | Increased completion and reduced ordering loss | Center-specific workflow |
| EVIDENCE MRD analysis | 175 resected stage II–IIIA EGFR patients, 1,352 samples | Landmark MRD+ DFS HR 4.44; longitudinal NPV 91.3%; median lead time 169 days | Prognostic; not MRD-randomized |
| Up-front NGS, US real world | 13,139 Flatiron patients | Median OS 20.9 mo (up-front NGS) vs 17.5 (up-front non-NGS) vs 18.2 (NGS after first-line start) | Observational; attributed mainly to targeted-therapy receipt |
| Matched-therapy use after broad profiling | 6,620 US patients with actionable findings | 10.4% underuse of first-line on-label options; 72.3% underuse of guideline-concordant off-label options; 8.6% guideline-discordant use | Claims/EHR-linked observational data |
Patient experience, palliative care, and safety¶
| Domain | Population/result | Estimate | Source |
|---|---|---|---|
| Early palliative care | 151 metastatic NSCLC patients | 12-wk FACT-L 98.0 vs 91.5; depression 16% vs 38%; aggressive end-of-life care 33% vs 54%; OS 11.6 vs 8.9 mo | PMID 20818875 |
| T-DXd ILD | DESTINY-Lung01 | Adjudicated drug-related ILD 26%, including fatal events | PMID 34534430 |
| CheckMate 816 severe AE | Neoadjuvant nivolumab-chemo vs chemo | Grade 3–4 treatment-related AE 33.5% vs 36.9% | PMID 35403841 |
| KEYNOTE-671 severe AE | Perioperative pembrolizumab vs placebo | Grade ≥3 treatment-related AE 44.9% vs 37.3% | PMID 37272513 |
| AEGEAN severe AE | Perioperative durvalumab vs placebo | Grade 3–4 treatment-related AE 42.4% vs 43.2% | PMID 37870974 |
| SYMPRO-Lung post hoc survival | Weekly PRO monitoring vs usual care, stage I–IV (n=446) | Median OS 26 vs 21 mo; adjusted HR 0.80 (0.63–1.00) | Post hoc; stepped-wedge cluster design |
| Financial toxicity meta-analysis | 18 observational studies | Pooled proportion 0.55 (0.43–0.66; 8 studies) | Definitions heterogeneous |
Known conflicts and caveats¶
| Conflict | Why estimates differ | Rule for reuse |
|---|---|---|
| Adenocarcinoma burden | Registry histology coverage, imputation, diagnostic era | Keep model, year, sex, and geography |
| Never-smoker fraction | Definition, geography, sex, referral enrichment | Do not quote a universal percentage without denominator |
| Screening harms | Positivity threshold, volumetry, round, work-up algorithm | Keep trial/program and definition |
| Driver frequency | Ancestry, smoking, stage, assay, tissue adequacy | Never use phenotype to skip testing |
| PFS across targeted trials | Line, comparator, CNS eligibility, follow-up | No cross-trial ranking |
| PD-L1 | Assay, cutoff, biopsy site, treatment exposure | Record clone, score, specimen, date |
| MRD sensitivity | Tumor burden, shedding, assay and sampling time | Negative is not proof of cure |
| Perioperative EFS | Stage editions and therapy architecture differ | Do not infer adjuvant-component value |
| OS | Crossover and subsequent therapies vary | Report treatment switching and follow-up |
Reuse checklist¶
- Preserve population, histology, stage, genotype, and line.
- Preserve comparator, endpoint, time point, and confidence interval.
- Label randomized, single-arm, observational, or modelled evidence.
- Do not average conflicting estimates.
- Re-query living guidelines and trial status at use.
- Reproduce derived values only with the original numerator and denominator.