Abstract 4600
Background
New patterns of response to ICIs were recently described, including hyperprogressive disease (HPD) and pseudoprogression (PsPD). However, there is a lack of unanimous criteria about its definition. HPD predictors have not been identified. We aim to characterize predictive variables and related outcomes of patients (pts) treated with ICIs experiencing rapid tumor surge at our institution.
Methods
We performed a retrospective analysis of 210 pts treated with mono or dual ICI or ICI plus chemotherapy (CHT), from November 2013 to October 2018. Two CT scans before ICI and 1 CT scan while treatment was required and assessed according to RECIST 1.1. Tumor growth rate (TGR) at baseline, during ICI and its variation per month (ΔTGR) were calculated. HPD was defined as ΔTGR ≥ 2-fold. Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method and compared between HPD and not HPD using the log-rank test.
Results
187 pts were eligible, 23 pts died before tumor assessment. Mean age 63 (37-83), male 75%, performance status (PS) ≤1 88%. Non-small cell lung cancer (NSCLC) 62%, urothelial carcinoma 23% and kidney carcinoma 15%. Treated in phase3 31%. Two or more prior treatment lines (TL) 24%, ICI monotherapy 85% (nivolumab 49%, pembrolizumab 28%, atezolizumab 22%) and 11% combined with CHT. More than 3 metastatic sites 28%. At first evaluation 29 pts (15.5%) had progressive disease: 18 pts (10%) met HPD criteria; while 11 pts (6%) had ΔTGK < 2 (6 confirmed PsPD and 5 received a new TL before a second CT). Only 5 pts (3%) had dissociated response and 3 (2%) progressed within 4 months. Median OS was significantly shorter in HPD compared to non-HPD group: 4.65 vs. 11.3 months, p < 0.005 (HR 2.11; CI95% 1.25 − 3.57). A sub-analysis by tumor type showed worse OS in every group, but statistical significance in NSCLC. Median PFS was lower in HPD vs. non-HPD (2.25 vs 3.97 months, p < 0.001). No differences according to age, gender, PS, number of TL, type of ICI, tumor type or number of metastatic sites were identified.
Conclusions
In our multitumor cohort, HPD occurs in 10% of pts treated with ICIs and is associated with worse OS, mostly in NSCLC. Further work is needed to better characterize this population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Ghiglione: Travel / Accommodation / Expenses: Kyowa Kirin; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Rovi; Travel / Accommodation / Expenses: Leo Pharma; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Lilly. C. Cabrera Galvez: Advisory / Consultancy: Pfyzer; Advisory / Consultancy: Roche ; Advisory / Consultancy: Boehringer ; Advisory / Consultancy: Ingelheim; Advisory / Consultancy: Bristol-Myers Squibb. O. Reig: Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Pfizer; Travel / Accommodation / Expenses: Ipsen. N. Viñolas: Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Viphor Pharma; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Pierre Fabre. A. Prat: Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Nanostring Technology ; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Oncolytics Biotech ; Honoraria (self), Speaker Bureau / Expert testimony: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Puma ; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb. B. Mellado: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb. N. Reguart: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche ; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AbbVie; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis ; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly ; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Aztra Zeneca ; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Guardiant Health ; Research grant / Funding (self): Instituto Carlos III ; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen. All other authors have declared no conflicts of interest.
Resources from the same session
2115 - Preclinical in vivo screening to predict responder patients depend on EGFR status
Presenter: Yejin Kim
Session: Poster Display session 3
Resources:
Abstract
3349 - Interplay between miR-17-5p and MALAT-1 Shapes The Cytokine Storm in Triple Negative Breast Cancer (TNBC) Tumor Microenvironment
Presenter: Raghda Soliman
Session: Poster Display session 3
Resources:
Abstract
4014 - Clinical verification on the relationship between lipid metabolism and the immune microenvironment of breast cancer
Presenter: Wataru Goto
Session: Poster Display session 3
Resources:
Abstract
4158 - The clinical and transcriptional signatures of human CD204 reveal an applicable marker for tumor associated macrophage in breast cancer
Presenter: Yunjie He
Session: Poster Display session 3
Resources:
Abstract
5392 - Activated effector T cells co-expressing multiple inhibitory receptors (IRs) are enriched in the tumor immune microenvironment in high grade serous ovarian cancer (HGSOC)
Presenter: Alice Bergamini
Session: Poster Display session 3
Resources:
Abstract
2617 - Oncolytic reovirus as a new anti-tumor strategy in castration resistant prostate cancer
Presenter: Yunlim Kim
Session: Poster Display session 3
Resources:
Abstract
2995 - Dysregulation of helper T lymphocytes in esophageal squamous cell carcinoma (ESCC) patients is highly associated with aberrant production of miR-21
Presenter: Ali Memarian
Session: Poster Display session 3
Resources:
Abstract
3597 - Myeloid derived suppressor cells but not regulatory T cells are associated with adaptive immunity and clinical outcomes in anal squamous cell carcinoma
Presenter: Christophe Borg
Session: Poster Display session 3
Resources:
Abstract
3430 - Evaluation of immune responses among responders (R) and non-responders (non-R) in a humanized mouse model with colorectal cancer (CRC) xenografts treated with combination immunotherapy
Presenter: Juan Marín Jiménez
Session: Poster Display session 3
Resources:
Abstract
1995 - ¬¬Advanced melanoma patients with high CD16+ macrophages have better response and survival to anti-PD-1 based immunotherapy
Presenter: Hansol Lee
Session: Poster Display session 3
Resources:
Abstract