Title |
Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1
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Published in |
Clinical Cancer Research, April 2017
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DOI | 10.1158/1078-0432.ccr-16-1741 |
Pubmed ID | |
Authors |
Stéphane Champiat, Laurent Dercle, Samy Ammari, Christophe Massard, Antoine Hollebecque, Sophie Postel-Vinay, Nathalie Chaput, Alexander Eggermont, Aurélien Marabelle, Jean-Charles Soria, Charles Ferté |
Abstract |
Purpose While Immune checkpoint inhibitors are disrupting the management of cancer patients, anecdotal occurrences of rapid progression (i.e. hyperprogressive disease or HPD) under these agents have been described, suggesting potentially deleterious effects of these drugs. The prevalence, the natural history and the predictive factors of HPD in cancer patients treated by anti PD-1/PD-L1 remain unknown. Experimental design Medical records from all patients (N =218) prospectively treated in Gustave Roussy by anti PD-1/PD-L1 within phase I clinical trials were analyzed. The tumor growth rate (TGR) prior ("REFERENCE") and upon ("EXPERIMENTAL") anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR, clinico-pathological characteristics and overall survival (OS) were computed. Results HPD was defined as a RECIST progression at the first evaluation and as a ≥ two-fold increase of the TGR between the REF and the EXP periods. Out of 131 evaluable patients, 12 patients (9%) were considered as HPD. HPD was not associated with higher tumor burden at baseline, nor with any specific tumor type. At progression, HPD patients had a lower rate of new lesions than progressive non-HPD patients (p<0.05). HPD is associated with a higher age (p<0.05) and a worse outcome (Overall Survival). Interestingly, REFERENCE TGR (before treatment) was inversely correlated with response to anti-PD-1/PD-L1 (P<0.05). Conclusion A novel aggressive pattern of hyper-progression exists in a fraction of patients treated with anti-PD-1/PD-L1. This observation raises potentially some concerns about treating elderly patients (>65 y.o) with anti-PD-1/PD-L1 monotherapy. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 33 | 21% |
Spain | 20 | 13% |
France | 15 | 10% |
United Kingdom | 4 | 3% |
Australia | 3 | 2% |
Japan | 3 | 2% |
Switzerland | 3 | 2% |
Canada | 3 | 2% |
China | 2 | 1% |
Other | 8 | 5% |
Unknown | 62 | 40% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 89 | 57% |
Scientists | 35 | 22% |
Practitioners (doctors, other healthcare professionals) | 32 | 21% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
France | 1 | <1% |
Austria | 1 | <1% |
Unknown | 564 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 130 | 23% |
Student > Ph. D. Student | 67 | 12% |
Other | 60 | 11% |
Student > Master | 47 | 8% |
Student > Bachelor | 35 | 6% |
Other | 100 | 18% |
Unknown | 128 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 211 | 37% |
Biochemistry, Genetics and Molecular Biology | 73 | 13% |
Agricultural and Biological Sciences | 41 | 7% |
Immunology and Microbiology | 27 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 16 | 3% |
Other | 45 | 8% |
Unknown | 154 | 27% |