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
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract