Hyperprogressive disease in early-phase immunotherapy trials: Clinical predictors and association with immune-related toxicities.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Clinical Trials as Topic
Disease Progression
Female
Humans
Immunotherapy
/ adverse effects
Male
Middle Aged
Neoplasms
/ diagnostic imaging
Prognosis
Sex Factors
Tomography, X-Ray Computed
Treatment Outcome
Young Adult
adverse events
hyperprogressive disease
immunotherapy
toxicities
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
15 04 2019
15 04 2019
Historique:
received:
22
10
2018
revised:
21
11
2018
accepted:
03
12
2018
pubmed:
16
2
2019
medline:
15
1
2020
entrez:
16
2
2019
Statut:
ppublish
Résumé
A subset of patients treated with immune checkpoint inhibitors experience an accelerated tumor growth rate (TGR) in comparison with pretreatment kinetics; this is known as hyperprogression. This study assessed the relation between hyperprogressive disease (HPD) and treatment-related toxicity and clinical factors. This study reviewed patients with solid tumors who were enrolled in early-phase immunotherapy trials at Princess Margaret Cancer Centre between August 2012 and September 2016 and had computed tomography scans in the pre-immunotherapy (reference) and on-immunotherapy (experimental) periods. HPD was defined as progression according to Response Evaluation Criteria in Solid Tumors 1.1 at the first on-treatment scan and a ≥2-fold increase in TGR between the reference and experimental periods. Treatment-related toxicities requiring systemic therapy, drug delays, or discontinuation were considered clinically significant adverse events (CSAEs). Of 352 patients, 182 were eligible for analysis. The median age was 60 years, and 54% were male. The Eastern Cooperative Oncology Group performance status was 0 (32%) or 1 (68%). The Royal Marsden Hospital (RMH) prognostic score was 0/1 in 59%. Single-agent immunotherapy was given to 80% of the patients. Most patients (89%) received anti-programmed death (ligand) 1 antibodies alone or in combination with other therapies. HPD occurred in 12 of 182 patients (7%). A higher proportion of females was seen among HPD patients (P = .01), but no association with age, performance status, tumor type, RMH prognostic score, combination immunotherapy, or CSAEs was found. The 1-year overall survival rate was 28% for HPD patients and 53% for non-HPD patients (hazard ratio, 1.7; 95% confidence interval, 0.9-3.3; P = .11). HPD was observed in 7% of patients with solid tumors treated with immunotherapy. HPD was not associated with CSAEs, age, tumor type, or the type of immunotherapy but was more common in females.
Sections du résumé
BACKGROUND
A subset of patients treated with immune checkpoint inhibitors experience an accelerated tumor growth rate (TGR) in comparison with pretreatment kinetics; this is known as hyperprogression. This study assessed the relation between hyperprogressive disease (HPD) and treatment-related toxicity and clinical factors.
METHODS
This study reviewed patients with solid tumors who were enrolled in early-phase immunotherapy trials at Princess Margaret Cancer Centre between August 2012 and September 2016 and had computed tomography scans in the pre-immunotherapy (reference) and on-immunotherapy (experimental) periods. HPD was defined as progression according to Response Evaluation Criteria in Solid Tumors 1.1 at the first on-treatment scan and a ≥2-fold increase in TGR between the reference and experimental periods. Treatment-related toxicities requiring systemic therapy, drug delays, or discontinuation were considered clinically significant adverse events (CSAEs).
RESULTS
Of 352 patients, 182 were eligible for analysis. The median age was 60 years, and 54% were male. The Eastern Cooperative Oncology Group performance status was 0 (32%) or 1 (68%). The Royal Marsden Hospital (RMH) prognostic score was 0/1 in 59%. Single-agent immunotherapy was given to 80% of the patients. Most patients (89%) received anti-programmed death (ligand) 1 antibodies alone or in combination with other therapies. HPD occurred in 12 of 182 patients (7%). A higher proportion of females was seen among HPD patients (P = .01), but no association with age, performance status, tumor type, RMH prognostic score, combination immunotherapy, or CSAEs was found. The 1-year overall survival rate was 28% for HPD patients and 53% for non-HPD patients (hazard ratio, 1.7; 95% confidence interval, 0.9-3.3; P = .11).
CONCLUSIONS
HPD was observed in 7% of patients with solid tumors treated with immunotherapy. HPD was not associated with CSAEs, age, tumor type, or the type of immunotherapy but was more common in females.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1341-1349Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 American Cancer Society.