While cancer immunotherapy continues to show promise in improving outcomes for patients across several tumor types, we must collectively strive to potentiate and personalize this armory to successfully unleash the power of the immune system in a greater number of individuals to attack disease. As importantly, research must continue to deliver robust immune data to better gauge which patients would most likely benefit from these immune-based therapies, those who will not, and as crucially, identify those who may suffer ​potential deleterious effects upon treatment.

Over recent years, increasing case reports and retrospective series have shown that these novel anti-cancer medicines may accelerate disease progression in certain patients; so-termed hyperprogressive disease. This phenomenon brings with it several questions surrounding how best to assess disease response in patients treated with immunotherapy. Hyperprogession disease (HPD) with immune checkpoint inhibitors (ICIs) has recently been described as progression disease (PD) by response evaluation criteria in solid tumors (RECIST) with a ≥ two-fold increase in tumor growth rate experimental versus reference. The implementation of this assessment in clinical practice is however challenging since a previous CT scan is required to establish the rate of growth prior to the beginning of treatment.

Based on previous research led by VHIO’s Ignacio Matos Phase I Investigator of VHIO’s Early Clinical Drug Development Group and Associate Investigator of our Research Unit for Molecular Therapy of Cancer (UITM) – “la Caixa” – both of which are directed by Elena Garralda- which showcased during last year’s Meeting of the American Society of Clinical Oncology (ASCO), a tour de force team of VHIO clinical investigators are the first to have evaluated how HPD with ICIs therapy can be more faithfully captured based on RECIST 1.1 criteria.

Published as an open access Research Article* last week in Clinical Cancer Research, the researchers have reported that that while the radiological definition of HPD following both tumor growth criteria (TGR) and RECIST, occurs in patients treated with targeted agents as well as those receiving ICIs in VHIO’s phase I trials carried out at the UITM, significant overall survival difference was only observed with RECIST criteria in the latter group.

“Having assessed almost 300 patients treated with immune checkpoint inhibitors in phase I trials conducted at VHIO’s phase I Unit, our Research Unit for Molecular Therapy of Cancer (UITM) – “la Caixa”, we have established a new definition that can be more easily applied to the clinic. Our approach in capturing hyperprogressive disease in these patients is as intuitive as it is easy to use in daily clinical practice. Our findings consequently represent an important forward step in better guiding treatment decisions for these patients,” observed First Author of the present study, Ignacio Matos.

“We can now more effectively identify those patients who do not show any benefit from treatment with immunotherapy. Importantly, our definition correlates with poor overall survival and represents a clear contra-indication for treatment beyond progression,” added Elena Garralda, Co-Corresponding Author of this timely paper.

Also reflective of the relevance of this research, Ignacio was awarded a one-year Translational Focus Fellowship from the European Society for Medical Oncology (ESMO) at ESMO Congress 2019: Translating science into better patient care, 27 September – 01 October, celebrated here in Barcelona. More specifically, under the mentorship of Sergio Quezada, Professor of Cancer Immunology and Immunotherapy at UCL Cancer Institute, London, UK, Ignacio will pursue research on the Impact of human FCγR gene polymorphism on hyper-progression disease with anti-PD1 inhibitors based on Antibody mediated PD1+ T cell phagocytosis.

###

Reference:

* Matos I, Martin-Liberal J, Garcia-Ruiz A, Hierro C, Ochoa de Olza M, Viaplana C, Azaro A, Vieito M, Brana I, Mur G, Ros J, Mateos J, Villacampa G, Berché R, Oliveira M, Alsina M, Élez E, Oaknin A, Muñoz-Couselo E, Carles J, Felip E, Rodon J, Tabernero J, Dienstmann R, Perez-Lopez R, Garralda E. Capturing Hyperprogressive disease with immune checkpoint inhibitors using RECIST 1.1 criteria. Clin Cancer Res. 2019 Nov 22. pii: clincanres.2226.2019. doi: 10.1158/1078-0432.CCR-19-2226.