Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response
| Autor: | Thomas F. Gajewski, Evan J. Lipson, Tricia R. Cottrell, F.S. Hodi, Julie E. Stein, Megan Wind-Rotolo, Janis M. Taube, Shailender Bhatia, Abha Soni, Robin Edwards, Liudmila V Danilova, William H. Sharfman, W J Urba |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Neoplasm Residual Skin Neoplasms Necrosis Biopsy Programmed Cell Death 1 Receptor H&E stain Kaplan-Meier Estimate Antibodies Monoclonal Humanized 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Stable Disease Major Pathologic Response Fibrosis Internal medicine Biomarkers Tumor medicine Humans Prospective Studies Melanoma Response Evaluation Criteria in Solid Tumors Aged Skin medicine.diagnostic_test business.industry Original Articles Hematology Middle Aged medicine.disease Ipilimumab Nivolumab 030104 developmental biology 030220 oncology & carcinogenesis Biomarker (medicine) Female medicine.symptom business |
| Zdroj: | Annals of Oncology. 30:589-596 |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdz019 |
| Popis: | BACKGROUND: With increasing anti-PD-1 therapy use in patients with melanoma and other tumor types, there is interest in developing early on-treatment biomarkers that correlate with long-term patient outcome. An understanding of the pathologic features of immune-mediated tumor regression is key in this endeavor. MATERIALS AND METHODS: Histologic features of immune-related pathologic response (irPR) following anti-PD-1 therapy were identified on hematoxylin and eosin (H&E)-stained slides in a discovery cohort of pre- and on-treatment specimens from n = 16 patients with advanced melanoma. These features were used to generate an irPR score [from 0 = no irPR features to 3 = major pathologic response on biopsy (MPR(bx), ≤10% residual viable tumor)]. This scoring system was then tested for an association with objective response by RECIST1.1 and overall survival in a prospectively collected validation cohort of pre- and on-treatment biopsies (n = 51 on-treatment at 4-week timepoint) from melanoma patients enrolled on the nivolumab monotherapy arm of CA209-038 (NCT01621490). RESULTS: Specimens from responders in the discovery cohort had features of immune-activation (moderate–high TIL densities, plasma cells) and wound-healing/tissue repair (neovascularization, proliferative fibrosis) compared to nonresponders, (P ≤ 0.021, for each feature). In the validation cohort, increasing irPR score associated with objective response (P = 0.009) and MPR(bx) associated with increased overall survival (n = 51; HR 0.13; 95%CI, 0.054–0.31, P = 0.015). Neither tumoral necrosis nor pretreatment histologic features were associated with response. Eight of 16 (50%) of patients with stable disease showed irPR features, two of which were MPR(bx), indicating a disconnect between pathologic and radiographic features at the 4-week on-therapy timepoint for some patients. CONCLUSIONS: Features of immune-mediated tumor regression on routine H&E-stained biopsy slides from patients with advanced melanoma correlate with objective response to anti-PD-1 and overall survival. An on-therapy biopsy may be particularly clinically useful for informing treatment decisions in patients with radiographic stable disease. This approach is inexpensive, straightforward, and widely available. |
| Databáze: | OpenAIRE |
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