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Baseline tumor size as an independent prognostic factor for overall survival in patients with metastatic melanoma treated with the anti-PD-1 monoclonal antibody MK-3475.
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2014
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Cancer ManagementPrognosisImmunologyPathologyOverall SurvivalBinary Tree AnalysisOncologyRadiation OncologyCancer ResearchMolecular OncologyBaseline Tumor SizeMelanomaMetastatic MelanomaMedian OsCancer TreatmentPrognostic EvaluationCancer EpidemiologyImmune Checkpoint InhibitorMedicine
3015 Background: We explored baseline tumor size (BTS) as a prognostic factor in addition to standard prognostic variables for overall survival (OS) in pts with metastatic melanoma treated with MK-3475. Methods: In a phase I clinical trial, 411 pts received MK-3475 2 mg/kg Q3W, 10 mg/kg Q3W, or 10 mg/kg Q2W. Response was assessed every 12 wk by RECIST 1.1 by independent central review. BTS was quantified as the sum of the longest dimensions of all RECIST target lesions. Log-rank, Kaplan-Meier (KM), and Cox proportional hazards regressions were used to identify independent prognostic factors for OS. Cutpoints and combinations of prognostic factors were determined by binary tree analysis. Results: Of the 411 melanoma pts studied, 365 had measurable tumors at baseline and a median follow-up duration of 10 mo as of the 10/18/2013 cutoff date. Median OS was not reached, and 1-y OS was 71% in all 411 pts and 69% in the 365 pts included in this analysis. By univariate analysis, the following traditional factors were associated with OS: elevated LDH, ECOG performance status of 1, and M-stage 1c (Table). BTS (median 97.8 mm, range 10.4-895 mm) was significantly and strongly associated with OS using log-rank tests, Cox models, KM methods, and binary tree analysis. Binary tree analysis provided a cutpoint of 90 mm BTS as an independent factor. While tumor size >90 mm was associated with a worse prognosis, these pts did have a median OS of 14 mo in the combined data set, suggesting they derive benefit from MK-3475. Conclusions: Baseline tumor size is the strongest independent prognostic factor in pts with metastatic melanoma treated with MK3475. If further validated, baseline tumor size could serve as an additional factor when randomizing pts for future clinical trials using anti-PD1 therapies. Clinical trial information: NCT01295827. N = 363 n % Alive at 1 Year [95% CI] HR P value LDH Elevated 135 54.8 [37.8-71.9] 2.33 <0.001 Normal 225 77.2 [69.6-84.9] M-Stage M1c 213 64.9 [54.2-75.6] 1.56 <0.05 Not M1c 152 75.4 [65.5-85.4] ECOG performance status 0 261 74.6 [66.8-82.3] 2.23 <0.001 1 104 55.5 [36.5-74.4] Baseline tumor size >90 194 54.8 [40.4-69.2] 3.51 <0.001 ≤90 171 84.3 [77.4-91.3]