biostudies-literatureCortellini ANational Institute for Health Research (NIHR)Wellcome Trust9https://www.ebi.ac.uk/biostudies/studies/S-EPMC8780322biostudies-literatureUnknown15(1)Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case-control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46-0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48-0.89]; p = 0.0074) and higher disease control raJournal of hematology & oncologyHigh familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status.PMC8780322PS3416Mazzoni FGelibter AAddeo ASantini DGuida AGiusti RRastelli FPecci FGenova CButi SRusso AFiletti MDe Tursi MChiari RBerardi RMorabito ANigro ORicciardi STuzi AMansueto GGhidini MBria EAerts JGJVDella Gravara LMacerelli MBertolini FGrossi FZoratto FFicorella CFriedlaender AGori SMigliorino MRDi Marino PMetro GCortellini AMarchetti PFerrara MGPorzio GCantini LBanna GLSpinelli GPDi Maio MAntonuzzo LRussano MTiseo MCitarella FAdamo VPinato DJPassiglia FfalseHigh familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status.Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case-control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46-0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48-0.89]; p = 0.0074) and higher disease control ra2022-01-01T00:00:00Z2022 Jan2025-05-29T22:27:29.229Z2025-05-29T22:27:29.229ZS-EPMC87803223506299310.1186/s13045-022-01226-2