Abstract 3033
Background
Immunotherapy (IO) has improved the outcome of metastatic non-small cell lung cancer (mNSCLC), but only a minority of patients (pts) derives a benefit from treatment (tx). Recent evidences supported a role of gut flora in influencing systemic response against tumors. The use of antibiotics (Abs) may impair the balance of microbiota and negatively affect the efficacy of IO. We aimed at analyzing this topic in a cohort of mNSCLC pts.
Methods
Data about all consecutive mNSCLC pts treated with IO at Istituto Nazionale dei Tumori, Milan, Italy, from 04/2013 to 01/2018 were retrospectively collected. We considered relevant for the analysis the use of Abs between 1 month (mo) before and 3 mos after the beginning of IO. We also evaluated the variable “Ab exposure” (AE), defined as the % “days of ab tx/days of IO”. Survival was estimated with Kaplan-Meier method; curves were compared with log-rank test. Cox proportional model was used for multivariate analyses.
Results
We identified 157 cases. Most pts had a performance status (PS) ECOG ≥1 (52.2%) and ≥2 sites of metastatic disease (86.0%). IO was either an anti-PD1 (62.4%), an anti-PDL1 (32.5%), or a combination anti-PDL1/CTLA4 (5.1%); it was prescribed in first line in 25 pts, in second line in 66 pts, in a more advanced lines in 66 pts. Abs were administered to 27 pts, mostly for pneumonia. The most common were levofloxacin (55.6%), amoxi-clavulanate (25.9%) and ceftriaxone (14.8%). Progression free survival (PFS) and overall survival (OS) did not differ between Ab-treated and Ab-untreated pts (p.18; p.24, respectively). Median AE of the Ab-treated pts was 4.3% (range 0.6%-42.9%). Both PFS and OS were significantly lower in pts with a higher AE than the median one (2.2 vs 7.7 mos, p<.0001; 4.9 vs 16.3 mos, p.0004, respectively). At multivariate analysis with the other significant variables (PS and IO line), the impact of AE on PFS and OS retained significance (p.0003; p.0002, respectively).
Conclusions
These results suggest that the length of Ab tx, rather than their simple use in a defined time frame, may impair the efficacy of IO. Further research is needed to support this evidence. However, it may be advisable to carefully evaluate the prescription of long Ab cycles to mNSCLC pts receiving IO.
Clinical trial identification
Legal entity responsible for the study
Istituto Nazionale dei Tumori.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
M. Imbimbo: Honoraria: BMS. C. Proto: Honoraria: BMS, MSD, Eli Lilly. D. Signorelli: Honoraria: AstraZeneca, Boehringer Ingelheim, BMS. M.C. Garassino: Honoraria: Roche, AstraZeneca, Boehringer Ingelheim. G. Lo Russo: Honoraria: Eli Lilly, BMS, AstraZeneca. All other authors have declared no conflicts of interest.
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