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
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract