4600 - Patterns and outcomes related to rapid progressive disease in a cohort of advanced solid tumors treated with immune checkpoint inhibitors (ICIs).

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.