New patterns of progression under immune checkpoint targeted (ICT) monoclonal antibodies (mAb) have been described such as pseudoprogression (PsPD). Except for melanoma, variations between studies reveal difficulties to establish their real incidence. This study aims to assess different patterns of progression in ICT mAb phase I trials.
All patients participating in ICT mAb phase I trials at the Drug Development Department at Gustave Roussy for solid tumors excluding melanoma, were enrolled. Radiological evaluations according to iRECIST 1.1 were correlated with prospectively registered patient characteristics and outcomes.
Among 360 patients included between August 2015 and November 2017, 70.6% received ICT mAb combination: 58.3% with another ICT mAb, 27.9% with targeted therapy and 13.8% with radiotherapy. Patients received a median of 2 previous lines of therapy (range 0-10). The objective response rate was 17.2%. PsPD were observed in 10 (2.8%) of patients (1 NSCLC, 1 microsatellite-high colon cancer, 1 hepatocarcinoma, 2 renal, 2 bladder, 1 cervix, 1 thyroid and 1 thymic cancer). PsPD patients had a median PFS (until confirmed PD according to iRECIST) of 17.3 months (95%CI[4.8-N.R]) that was comparable to other responders patients PFS (median unreached 95%CI[13.8-N.R]; HR, 2.0; 95%CI[0.7-6.1]; p = 0.2). Dissociated responses (defined as a concomitant progressing and responding lesions) were reported for 4.2% of patients with a median PFS of 4.8 months (95%CI[3.0-15.6]) comparable to stable disease patients (median PFS 5.0 months 95%CI[4.3-6.4]; HR, 0.9; p = 0.6). Among the 203 patients who progressed at first evaluation, 139 (68%) were withdrawn from the phase I study at first assessment, whereas 64 (32%) continued ICT mAb and underwent another CT scan evaluation one-month later.
We showed a low rate of PsPD and dissociated response in a large cohort of patients excluding melanoma. Using iRECIST, 32% of progressing patients underwent another CT scan at one month confirming PD, which may delay the initiation of a new regimen. This work suggests that prognosis or on-treatment biomarkers are needed to identify early patients who should (or not) continue ICI treatment once a first progression is evidenced.
Clinical trial identification
Legal entity responsible for the study
Institut Gustave Roussy.
Has not received any funding.
A. Hollebecque: Honoraria: Merck Serono; Advisory role: Amgen, Lilly; Travel and accommodation expenses: Amgen, Servier. S. Postel-Vinay: Honoraria: AstraZeneca. A. Marabelle: Honoraria/consultancy fees: Medimmune, Lilly, Amgen, BMS, Merck Serono, Sanofi Genzyme, Janssen, Astellas, Genentech, Orion, Ipsen. J-C. Soria: Full time employed in Medimmune since September 2017; Consultancy fees in the last 2 years: AstraZeneca, Astex, Clovis, GSK, Gammamabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, Pharmamar, Pierre Fabre, Roche-Genentech, Sanofi, Servier, Symphogen, Takeda. C. Massard: Honoraria/consultancy fees: Sanofi Genzyme, Janssen, Astellas, Genentech, Orion, Medimmune, Ipsen. All other authors have declared no conflicts of interest.