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Comparative Study
. 2016 Nov 8;115(10):1186-1192.
doi: 10.1038/bjc.2016.308. Epub 2016 Oct 4.

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

Leila Khoja  1   2 , Minnie Kibiro  3 , Ur Metser  3 , Craig Gedye  1 , David Hogg  1 , Marcus O Butler  1 , Eshetu G Atenafu  4 , Anthony M Joshua  1
Affiliations
Comparative Study

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

Leila Khoja et al. Br J Cancer. .

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.

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Conflict of interest statement

DH serves on Advisory Boards for Roche, Merck, GlaxoSmithKline, Bristol-Myers Squibb and Novartis. CG has served on advisory boards for Novartis and Bristol-Myers Squibb. MB serves on Advisory Boards for Merck, Novartis, Bristol-Myeers Squibb and Immunovaccine. LK is currently an employee of AstraZeneca.

Figures

Figure 1
Figure 1
Response as assessed in individual lesions and according to location. (A) Overview of response of individual lesions, most lesions remained stable (34%) with CR evident in 25%. (B) Response differed according to location of metastatic disease with lung lesions showing the greatest response.
Figure 2
Figure 2
Patterns of response as assessed by (A) irRC and (B) Response evaluation criteria in solid tumors (RECIST) 1.1. Response patterns differed with greater variation seen on first scan as assessed by RECIST in comparison with irRC.
Figure 3
Figure 3
Serial images from a 62-year-old woman with metastatic melanoma to the subcutaneous tissues treated with anti-PD-1 antibody. (A) Baseline scan shows a subcutaneous deposit measuring 26 × 20 mm with a density of 57 HU. (B) The first follow-up scan performed 13 weeks after the first infusion and showed that the lesion had progressed by RECIST and irRC (measurements were 48 × 32 mm), but had decreased in density (to 38 HU). (C) On the second follow-up CT scan, the measurements were 60 × 31 mm, but the density had again decreased (to 35 HU). (D) On the final assessment scan, the measurements were 67 × 30 mm, but density was 25 HU.
See this image and copyright information in PMC

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