Ignacio Matos 1,2 , Juan Martin-Liberal 3 , Alonso García-Ruiz 4 , Cinta Hierro 3 , Maria Ochoa de Olza 3 , Cristina Viaplana 5 , Analia Azaro 3 , Maria Vieito 3 , Irene Braña 3 , Gemma Mur 6 , Javier Ros 3 , Jose Mateos 7 , Guillermo Villacampa 5 , Roger Berché 5 , Mafalda Oliveira 3 , Maria Alsina 3 , Elena Elez 3 , Ana Oaknin 3 , Eva Muñoz-Couselo 3 , Joan Carles 3 , Enriqueta Felip 3,2 , Jordi Rodón 3 , Josep Tabernero 3,2 , Rodrigo Dienstmann 5 , Raquel Perez-Lopez 4 , Elena Garralda 1 Show Affiliations »
Abstract
PURPOSE: Most hyperprogression disease (HPD) definitions are based on tumor growth rate (TGR). However, there is still no consensus on how to evaluate this phenomenon. PATIENTS AND METHODS: We investigated two independent cohorts of patients with advanced solid tumors treated in phase I trials with (i) programmed cell death 1 (PD-1)/PD-L1 antibodies in monotherapy or combination and (ii) targeted agents (TA) in unapproved indications. A Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-based definition of hyperprogression was developed. The primary endpoint was the assessment of the rate of HPD in patients treated with ICIs or TAs using both criteria (RECIST and TGR) and the impact on overall survival (OS) in patients who achieved PD as best response. RESULTS: Among 270 evaluable patients treated with PD-1/PD-L1 inhibitors, 29 PD-1/PD-L1-treated patients (10.7%) had HPD by RECIST definition. This group had a significantly lower OS (median of 5.23 months; 95% CI, 3.97-6.45) when compared with the non-HPD progressor group (median, 7.33 months; 95% CI, 4.53-10.12; HR = 1.73, 95% CI, 1.05-2.85; P = 0.04). In a subset of 221 evaluable patients, 14 (6.3%) were categorized as HPD using TGR criteria, differences in median OS (mOS) between this group (mOS 4.2 months; 95% IC, 2.07-6.33) and non-HPD progressors (n = 44) by TGR criteria (mOS 6.27 months; 95% CI, 3.88-8.67) were not statistically significant (HR 1.4, 95% IC, 0.70-2.77; P = 0.346). Among 239 evaluable patients treated with TAs, 26 (10.9%) were classified as having HPD by RECIST and 14 using TGR criteria in a subset of patients. No differences in OS were observed between HPD and non-HPD progressors treated with TAs. CONCLUSIONS: HPD measured by TGR or by RECIST was observed in both cohorts of patients; however, in our series, there was an impact on survival only in the immune-checkpoint inhibitor cohort when evaluated by RECIST. We propose a new way to capture HPD using RECIST criteria that is intuitive and easy to use in daily clinical practice. ©2019 American Association for Cancer Research.
PURPOSE: Most hyperprogression disease (HPD ) definitions are based on tumor growth rate (TGR ). However, there is still no consensus on how to evaluate this phenomenon. PATIENTS AND METHODS: We investigated two independent cohorts of patients with advanced solid tumors treated in phase I trials with (i) programmed cell death 1 (PD-1 )/PD-L1 antibodies in monotherapy or combination and (ii) targeted agents (TA) in unapproved indications. A Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-based definition of hyperprogression was developed. The primary endpoint was the assessment of the rate of HPD in patients treated with ICIs or TAs using both criteria (RECIST and TGR ) and the impact on overall survival (OS) in patients who achieved PD as best response. RESULTS: Among 270 evaluable patients treated with PD-1 /PD-L1 inhibitors, 29 PD-1 /PD-L1 -treated patients (10.7%) had HPD by RECIST definition. This group had a significantly lower OS (median of 5.23 months; 95% CI, 3.97-6.45) when compared with the non-HPD progressor group (median, 7.33 months; 95% CI, 4.53-10.12; HR = 1.73, 95% CI, 1.05-2.85; P = 0.04). In a subset of 221 evaluable patients , 14 (6.3%) were categorized as HPD using TGR criteria, differences in median OS (mOS) between this group (mOS 4.2 months; 95% IC, 2.07-6.33) and non-HPD progressors (n = 44) by TGR criteria (mOS 6.27 months; 95% CI, 3.88-8.67) were not statistically significant (HR 1.4, 95% IC, 0.70-2.77; P = 0.346). Among 239 evaluable patients treated with TAs , 26 (10.9%) were classified as having HPD by RECIST and 14 using TGR criteria in a subset of patients . No differences in OS were observed between HPD and non-HPD progressors treated with TAs . CONCLUSIONS: HPD measured by TGR or by RECIST was observed in both cohorts of patients ; however, in our series, there was an impact on survival only in the immune-checkpoint inhibitor cohort when evaluated by RECIST. We propose a new way to capture HPD using RECIST criteria that is intuitive and easy to use in daily clinical practice. ©2019 American Association for Cancer Research.
Entities: Chemical
Disease
Gene
Species
Year: 2019
PMID： 31757877 DOI： 10.1158/1078-0432.CCR-19-2226
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531