Patterns of response to anti-PD-1 treatment: an exploratory comparison of four radiological response criteria and associations with overall survival in metastatic melanoma patients

Research output: Contribution to journalArticlepeer-review

Authors

  • Minnie Kibiro
  • Ur Metser
  • Craig Gedye
  • David Hogg
  • Marcus O Butler
  • Eshetu G Atenafu
  • Anthony M Joshua

Colleges, School and Institutes

External organisations

  • University Health Network
  • Department of Medical Oncology, Academic Medical Center
  • University of Dundee

Abstract

BACKGROUND: Radiological assessment of response to checkpoint inhibitors remains imperfect. We evaluated individual lesion and inter-patient response by response evaluation (RECIST) 1.1, immune-related response criteria (irRC), CHOI and modified CHOI (mCHOI) and correlated response with overall survival (OS).

METHODS: Thirty-seven patients with 567 measurable lesions treated with pembrolizumab in the Keynote 001 trial were studied. Association of response with OS was determined.

RESULTS: Response varied according to site; lung lesions had the highest rate of complete response (69 out of 163 (42%) vs other sites 71 out of 404 (18%), P<0.0001). Delayed response post first scan was seen in 2 out of 37 (5%) deemed progressive (PD) by RECIST and 2 out of 14 (14%) deemed PD by irRC. Modified CHOI criteria showed response of 38% (14 out of 37). Change in tumour size and density on first follow-up assessment was associated with OS with each 1000 mm2 increase in tumour size from baseline increasing the hazard of dying by 25.9% (HR=1.259, (95% CI=1.116-1.420), P=0.0002). Similarly, each 20HU increase in density increased the HR by 15% (HR=1.15, (95% CI 1.045-1.260), P=0.004). Response defined by any criteria had superior OS (CHOI P=0.0084; mCHOI P=0.0183; irRC P<0.0001 and RECIST P=0.0003).

CONCLUSIONS: Response by any criterion was prognostic. Novel patterns of response and changes on treatment in tumour density suggest complex anti-tumour responses to immunotherapy.

Details

Original languageEnglish
Pages (from-to)1186-1192
Number of pages7
JournalBritish Journal of Cancer
Volume115
Issue number10
Publication statusPublished - 4 Oct 2016

Keywords

  • Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized/therapeutic use, Antineoplastic Agents/therapeutic use, Female, Humans, Male, Melanoma/drug therapy, Middle Aged, Programmed Cell Death 1 Receptor/metabolism, Response Evaluation Criteria in Solid Tumors, Retrospective Studies, Treatment Outcome