title: Prolonged Benefit from Ipilimumab Correlates with Improved Outcomes from Subsequent Pembrolizumab.
abstract: Patients with metastatic melanoma whose disease progresses on ipilimumab can clearly derive benefit from subsequent anti-programmed death-1 (PD-1). However, patients experience heterogeneous outcomes with ipilimumab, including rapid or delayed progression, and it is unclear whether patterns of ipilimumab progression influence subsequent clinical responses to anti-PD-1. We retrospectively reviewed data from 116 patients with metastatic melanoma who progressed on ipilimumab and were subsequently treated with pembrolizumab. The study objectives were to determine whether progression-free survival (PFS) with ipilimumab was associated with PFS, objective response rate (ORR), and clinical benefit rate (CBR; ORR + stable disease) with pembrolizumab. Patients with PFS ≥90 days after treatment with ipilimumab generally had superior outcomes with subsequent pembrolizumab treatment compared with patients with PFS <90 days (ORR, 49% vs. 35%, P = 0.12; CBR, 66% vs. 46%, P = 0.03). Patients with prolonged ipilimumab benefit (PFS ≥ 180 days) had excellent outcomes with pembrolizumab compared with rapid progressors (PFS < 45 days; ORR, 55% vs. 25%; CBR, 80% vs. 25%; median PFS, 249 vs. 50 days). Using logistic regression models, PFS with ipilimumab was independently correlated with response to pembrolizumab (odds ratio, 1.22; 95% CI, 1.02-1.51). This study shows that prolonged PFS with ipilimumab predicts excellent outcomes with subsequent pembrolizumab treatment, offering valuable prognostic information for clinicians. Cancer Immunol Res; 4(7); 569-73. ©2016 AACR.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Mayo Clinic, Jacksonville, Florida. Shreders.Amanda@mayo.edu.
authors.forename: Amanda
authors.initials: A
authors.lastname: Shreders
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Mayo Clinic, Jacksonville, Florida.
authors.forename: Richard
authors.initials: R
authors.lastname: Joseph
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Shilin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000187:drug effects*; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000074324:Ipilimumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; D060908:CTLA-4 Antigen; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab