Abstract 1068P
Background
Case reports and uncontrolled studies have shown great responses to CT in pts with solid tumors and hematological malignancies after IO drugs, suggesting a chemosensitization of the checkpoint inhibitors. We explored this effect in a prospective database of pts included in IO, tyrosine kinase inhibitor (TKI) or epigenetic agent (EPI) phase I trials.
Methods
All pts with solid tumors on phase I trials at VHIO are followed post-progression and CT response was assessed based on standard clinical practice. A propensity score-matched population (CT post-IO vs. CT-post TKI) adjusted for clinico-pathological factors that could influence response to CT and prognosis was identified. Endpoints were RECIST objective response rate (ORR) and progression-free survival (PFS).
Results
From 986 pts enrolled between 2010 and 2019, 132 received CT post-progression (post-IO in 55 [42%], post-TKI in 70 [53%] and post-EPI in 7 [5%]). Median age was 61y, 66% females, most common tumors were breast (22%), head & neck (12%), colorectal (10%) and melanoma (10%). Median prior lines in CT post-IO or CT post-EPI groups was 2 and in the CT post-TKI pts was 3 (P = 0.02). Partial response (PR) of 5% and stable disease of 38% were achieved with phase I trial drug. At post progression CT, ORR was 16.4% post-IO, 8.6% post-TKI and 14.3% post-EPI (P = 0.43). An unadjusted Cox model showed no differences in CT PFS across groups (2.4 months post-IO, 2.8 months post-TKI, and 10.3 months post-EPI; P > 0.14 all comparisons). Due to small numbers, post-EPI pts were excluded for PS analysis. Remaining post-IO (n = 55) and post-TKI (n = 55) PS-matched cohort showed no differences in CT ORR (odds ratio 1.96 in favor of post-IO, CI95% 0.6-6.3, P = 0.27) or CT PFS (hazard ratio 0.85 in favor of post-IO, CI95% 0.6-1.3; P = 0.44). In a multivariable model, predictors of PR with CT post-progression on phase I trials were breast cancer (OR = 16.3; p = 0.002) and clinical benefit while on the trials (OR = 5.18; p = 0.04).
Conclusions
This unbiased controlled cohort study, despite numerically higher ORR with CT post-IO vs. post-TKI, showed no significant PFS differences with rescue CT between the groups, questioning the chemosensitization effect of IO drugs across solid tumors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Vall d´Hebron Institute of Oncology.
Funding
Has not received any funding.
Disclosure
V. Galvão: Travel/Accommodation/Expenses: F. Hoffmann-La Roche Ltd. F.J. Ros Montañá: Advisory/Consultancy: Sanofi. G. Villacampa Javierre: Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy: AstraZeneca. I. Braña: Advisory/Consultancy: Orion Pharma; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Serono; Advisory/Consultancy: Rakutan Pharma; Speaker Bureau/Expert testimony: Roche. A.B. Azaro Pedrazzoli: Advisory/Consultancy: Orion Corporation. Amcure GmbH; Research grant/Funding (institution): Amcure GmbH. M. Vieito Villar: Advisory/Consultancy: Debio, Roche, TFS; Travel/Accommodation/Expenses: Roche, Merck-Serono. O. Saavedra Santa Gadea: Travel/Accommodation/Expenses: Kyowakirin; Travel/Accommodation/Expenses: Roche. A. Hernando-Calvo: Travel/Accommodation/Expenses: Kyowa Kirin. J. Carles: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Johnson & Johnson; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony: Asofarma; Travel/Accommodation/Expenses: Ipsen; Research grant/Funding (institution): AB Science; Research grant/Funding (institution): Aragon Pharmaceuticals; Research grant/Funding (institution): Arog Pharmaceuticals; Research grant/Funding (institution): INC; Research grant/Funding (institution): Aveo Pharmaceuticals; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): BN Immunotherapeutics INC; Research grant/Funding (institution): Boehringer Ingelheim España; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Cougar Biotechnology; Research grant/Funding (institution): Deciphera Pharmaceuticals; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): F. Hoffmann-La Roche; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Janssen-Cilag; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): Laboratories Leurquin Mediolanum. T. Macarulla Mercade: Honoraria (self), Advisory/Consultancy: Advance Medical HCMS; Honoraria (self), Advisory/Consultancy: Baxter; Honoraria (self), Advisory/Consultancy: Biolinerx; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genzyme; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: Lab Servier; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Qed Therapeutics; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Prime; Honoraria (self), Advisory/Consultancy: QED; Honoraria (self), Advisory/Consultancy: Sanofi - Aventis; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Aslan; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Hallozyme; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Merimarck; Research grant/Funding (institution): Millenim; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pharmacyclics; Research grant/Funding (institution): Roche. E. Munoz Couselo: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi. E. Elez: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: F. Hoffmann-La Roche Ltd; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Servier; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Array; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Honoraria (institution): MSD; Honoraria (institution): AbbVie; Honoraria (institution): GSK; Honoraria (institution): AstraZeneca; Honoraria (institution): Novartis; Honoraria (institution): Boehringer Ingelheim. E. Felip: Advisory/Consultancy: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Janssen; Speaker Bureau/Expert testimony: Medscape; Advisory/Consultancy: Merck Kgaa; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Prime Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Samsung; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Touchime; Advisory/Consultancy: GSK; Advisory/Consultancy: Bayer; Research grant/Funding (institution): GOI; Research grant/Funding (institution): Fundación Merck Salud. J. Tabernero: Advisory/Consultancy: Array Biopharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Beigene; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Chugai; Advisory/Consultancy: Genentech; Advisory/Consultancy: Genmab; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Imugene; Advisory/Consultancy: Inflection Biosciences; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Kura; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Menarini; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Merus; Advisory/Consultancy: Molecular Partners; Advisory/Consultancy: Novartis; Advisory/Consultancy: Peptomyc; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Pharmacyclics; Advisory/Consultancy: Proteodesign; Advisory/Consultancy: Rafael Pharmaceuticals; Advisory/Consultancy: F Hoffmann-La Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Seagen; Advisory/Consultancy: Seattle Genetics. R. Dienstmann: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony, Research grant/Funding (self): Merck Sharp & Dohme; Research grant/Funding (self): Pierre Fabre. M. Oliveira: Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Speaker Bureau/Expert testimony: Novartis; Honoraria (institution), Advisory/Consultancy: GSK; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics; Honoraria (institution), Advisory/Consultancy: Puma; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution): Philips; Honoraria (institution): Genentech; Honoraria (institution): Zenith Epigenetics; Honoraria (institution): Immunomedics; Honoraria (institution): Boehringer Ingelheim. E. Garralda: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche/Genentech; Advisory/Consultancy: F. Hoffmann-La Roche; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Neomed; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Janssen; Advisory/Consultancy: Seagen; Advisory/Consultancy: TFS; Advisory/Consultancy: Alkermes; Advisory/Consultancy, Speaker Bureau/Expert testimony: Thermo Fisher; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Menarini; Travel/Accommodation/Expenses: Glycotope. All other authors have declared no Conflicts of interest.