Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1.
Purpose:While immune checkpoint inhibitors are disrupting the management of patients with cancer, 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 patients with cancer 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"; REF) and upon ("EXPERIMENTAL"; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR, clinicopathologic characteristics, and overall survival (OS) were computed.Results:HPD was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods. Of 131 evaluable patients, 12 patients (9%) were considered as having HPD. HPD was not associated with higher tumor burden at baseline, nor with any specific tumor type. At progression, patients with HPD had a lower rate of new lesions than patients with disease progression without HPD (P< 0.05). HPD is associated with a higher age (P< 0.05) and a worse outcome (overall survival). Interestingly, REF TGR (before treatment) was inversely correlated with response to anti-PD-1/PD-L1 (P< 0.05) therapy.Conclusions:A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD-1/PD-L1. This observation raises some concerns about treating elderly patients (>65 years old) with anti-PD-1/PD-L1 monotherapy and suggests further study of this phenomenon.Clin Cancer Res; 23(8); 1920-8. ©2016 AACRSee related commentary by Sharon, p. 1879.
Département d'Innovation Thérapeutique et des Essais Précoces (DITEP), Gustave Roussy, Université Paris Saclay, Villejuif, France.|INSERM, U981, Villejuif, France.
Stéphane
S
Champiat
Département de l'Imagerie Médicale, Service de Médecine Nucléaire et d'Endocrinologie, Gustave Roussy, Université Paris Saclay, Villejuif, France.
Laurent
L
Dercle
Département de l'Imagerie Médicale, Service d'Imagerie Diagnostique, Gustave Roussy, Université Paris Saclay, Villejuif, France.
Samy
S
Ammari
Département d'Innovation Thérapeutique et des Essais Précoces (DITEP), Gustave Roussy, Université Paris Saclay, Villejuif, France.
Christophe
C
Massard
Département d'Innovation Thérapeutique et des Essais Précoces (DITEP), Gustave Roussy, Université Paris Saclay, Villejuif, France.
Antoine
A
Hollebecque
Département d'Innovation Thérapeutique et des Essais Précoces (DITEP), Gustave Roussy, Université Paris Saclay, Villejuif, France.|INSERM, U981, Villejuif, France.
Sophie
S
Postel-Vinay
Gustave Roussy, Université Paris Saclay, Laboratoire d'Immunomonitoring en Oncologie, Villejuif, France.|CNRS, UMS 3655, Villejuif, France.|INSERM, US23, Villejuif, France.|INSERM, Centre d'Investigation Clinique Biothérapie 1428, Villejuif, France.
Nathalie
N
Chaput
Gustave Roussy, Université Paris Saclay, Villejuif, France.
Alexander
A
Eggermont
Département d'Innovation Thérapeutique et des Essais Précoces (DITEP), Gustave Roussy, Université Paris Saclay, Villejuif, France.|INSERM, U1015, Villejuif, France.
Aurélien
A
Marabelle
Département d'Innovation Thérapeutique et des Essais Précoces (DITEP), Gustave Roussy, Université Paris Saclay, Villejuif, France. charles.ferte@gustaveroussy.fr jean-charles.soria@gustaveroussy.fr.|INSERM, U981, Villejuif, France.
Jean-Charles
JC
Soria
Département d'Innovation Thérapeutique et des Essais Précoces (DITEP), Gustave Roussy, Université Paris Saclay, Villejuif, France. charles.ferte@gustaveroussy.fr jean-charles.soria@gustaveroussy.fr.|Département de Cancérologie Cervico Faciale, Gustave Roussy, Université Paris Saclay, Villejuif, France.|INSERM, U1030, Villejuif, France.
Charles
C
Ferté
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D017321:Clinical Trials, Phase I as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D016016:Proportional Hazards Models; D055815:Young Adult
D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor