2408 - Immune checkpoint inhibitors (ICIs) as “chemotherapy (Ctx) sensitization” strategy in advanced solid tumors

Background

The anti-tumor activity of Ctx after ICIs has been poorly investigated in patients with refractory advanced solid tumors. A recent communication suggested that ICIs may sensitize Non-Hodgkin Lymphoma to subsequent Ctx (Nicole A, Carreau et al, ASH 2019) but a control arm with exposure to alternative non-ICI therapy was missing.

Methods

From a prospective cohort of patients (pts) treated with ICIs (n = 310) or targeted agents (TAs) (n = 281) in Phase I trials at Vall d´Hebron Institute Oncology in the last 7 years, 31 (10.0%) and 52 (18.5%) received Ctx within 4 months after exposure to ICIs or TA, respectively. The aim of this study was to compare response rate (RR) and progression free survival (PFS) of subsequent Ctx after ICIs versus TAs. A propensity score (PS) matched analysis was performed to adjust for clinical-pathological heterogeneity between cohorts.

Results

In the overall study population, RR with Ctx after ICIs included partial response (PR) in 5 pts (16.1%), stable disease (SD) in 6 pts (16.4%) and progressive disease (PD) in 20 pts (64.5%). When Ctx was given after TAs, we found PR in 4 pts (7.7%), SD in 18 pts (34.6%) and PD in 30 (57.7%). Differences in RR with Ctx after ICIs or TAs were not significant (p = 0.43). Factors linked with higher RR were number of previous treatment lines (OR 0.51, p = 0.05) and breast cancer vs. other malignancies (OR 5.54, p = 0.05). In PS matched cohorts adjusted for these factors, median PFS with Ctx after ICIs was 2.3 months (95% IC 1.8-5.3) and after TAs was 3.2 months (95% CI 2.3-5.3; HR 1.01, 95% IC 0.59-1.74; p = 0.96).

Conclusions

Despite the numerically higher RR with Ctx after exposure to ICIs versus TAs (16.4% versus 7.7%), differences were not statistically significant and did not associate with improved median PFS after adjusting for clinico-pathological determinants of response to Ctx in advanced solid tumors. Larger prospectively designed cohorts are needed to validate this hypothesis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Vall d´Hebron Institute of Oncology (VHIO).

Funding

Has not received any funding.

Disclosure

J. Martin-Liberal: Speaker Bureau / Expert testimony: Astellas; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre Fabre; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: ipsen. C. Hierro: Research grant / Funding (institution): Bayer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ignyta; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche. I. Brana: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): BMS; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (self): Celgene; Research grant / Funding (self): giknik; Research grant / Funding (self): GSK; Research grant / Funding (self): Janssen; Research grant / Funding (self): Kura; Honoraria (self): Novartis; Research grant / Funding (self): Orion; Research grant / Funding (institution): Pfizer. M. Vieito Villar: Travel / Accommodation / Expenses: Roche. C. Saura: Speaker Bureau / Expert testimony, .: Roche. T. Macarulla Mercade: Honoraria (self): Genzyme; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self): Tesario; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Shire; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Celgene; Advisory / Consultancy: QDE; Advisory / Consultancy, Travel / Accommodation / Expenses: H3B; Advisory / Consultancy: Baxalta; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Aslan; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (institution): Genentech. E. Muñoz-Couselo: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Roche. J. Tabernero: Honoraria (self), Josep Tabernero reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics.: Josep Tabernero reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limi. R. Dienstmann: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Symphogen; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (self): Merck. E. Garralda: Advisory / Consultancy: Roche; Advisory / Consultancy: Ellipses Pharma ; Advisory / Consultancy: Neomed; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Janssen Global Services; Speaker Bureau / Expert testimony: BMS; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Glycotope; Travel / Accommodation / Expenses: Menarini. All other authors have declared no conflicts of interest.