Baseline Tumor Size Is an Independent Prognostic Factor for Overall Survival in Patients with Melanoma Treated with Pembrolizumab

<b>Purpose:</b> The purpose of this study was to assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827).<b>Experimental Design:</b> BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal <i>P</i> values with no multiplicity adjustment describe the strength of observed associations.<b>Results:</b> Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this <i>post hoc</i> analysis. Median BTS was 10.2 cm (range, 1-89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites; all <i>P</i> ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44% vs. 23%; <i>P</i> < 0.001) and improved OS (HR, 0.38; <i>P</i> < 0.001). In multivariate analyses, BTS below the median remained an independent prognostic marker of OS (<i>P</i> < 0.001) but not ORR. In 459 patients with available tumor programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1-positive tumors were independently associated with higher ORR and longer OS.<b>Conclusions:</b> BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma. <i>Clin Cancer Res; 24(20); 4960-7. ©2018 AACR</i> <i>See related commentary by Warner and Postow, p. 4915</i>.