Abstract 1040P
Background
Immune checkpoints inhibitors (ICIs) alone or in combination (with chemotherapy or tyrosine kinase inhibitors) are the new standard of treatment in several solid tumors. The different impact of single concomitant drugs on the outcome of ICI treated patients is already known. The aim of our study was to evaluate the prognostic value of a “drug score” (DS), including three class of drugs able to modulate the microbiota, in metastatic cancer patients treated with ICIs.
Methods
We retrospectively enrolled advanced patients consecutively treated with ICI at our center from October 2013 to October 2018, correlating the DS with overall survival (OS, primary endpoint) and progression-free-survival (PFS, secondary endpoint).
Results
219 patients were enrolled. Primary tumors were: non-small cell lung cancer (NSCLC, 69.9%), melanoma (15.1%), renal cell carcinoma (9.1%), other cancers (5.5%). Median follow-up was 21.3 months. 12.3% and 33.8% of patients received antibiotics and corticosteroids within 30 days before first ICI administration, respectively; 47.9% of patients underwent treatment with pump protonic inhibitors (PPIs). The use of PPIs, corticosteroids or antibiotics was individually associated to decreased OS and PFS at the univariate analysis. Therefore, we developed a “drug score” including these three drugs. 37.9% of patients did not receive any drug (DS 0), 35.2% received only one drug (DS 1) and 26.9% received two/three drugs (DS 2). The impact of DS on both OS and PFS was evident: median OS was 19.4 months in DS 0 vs9.5 months in DS 1 vs2.7 months in DS 2 (p < 0.001), median PFS was 6.8 months in DS 0 vs3.7 months in DS 1 vs 1.6 in DS 2 (p< 0.001). On multivariate analysis, only the comparison between DS 2 vsDS 0 resulted statistically significant, both in terms of OS [HR 1.88 (95%CI 1.18-3.01), p= 0.0082] and PFS [HR 2.12 (95%CI 1.33-3.38), p= 0.0017].
Conclusions
Our results confirmed the negative prognostic role of PPIs, corticosteroids and antibiotics either as single agents and included in the DS, probably due to the impact of these drugs on gut and lung microbiota. DS will be validated in an extended multicenter retrospective cohort including patients with metastatic NSCLC treated with ICIs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University Hospital of Parma.
Funding
Has not received any funding.
Disclosure
M. Bersanelli: Research grant/Funding (self): Seqirus; Research grant/Funding (self): Roche; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Novartis; Research grant/Funding (self): BMS; Research grant/Funding (self): Sanofi; Research grant/Funding (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Pfizer; Honoraria (self): Seqirus; Honoraria (self): Ipsen; Honoraria (self): AstraZeneca; Honoraria (self): Novartis. A. Cortellini: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Astellas; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): BMS; Research grant/Funding (self): MSD; Research grant/Funding (self): Novartis. M. Tiseo: Speaker Bureau/Expert testimony, Research grant/Funding (self): Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Takeda. S. Buti: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. All other authors have declared no conflicts of interest.