Influence Of Antibiotic Therapy (Atb) On Oncological Outcomes Of Metastatic Non-Small Cell Lung Cancer (Mnsclc) Patients Treated With Chemoimmunotherapy (Cit).

3080 Background: ATB exposure is proven to worsen response and survival in immunotherapy recipients. However, its influence on outcomes from CIT is currently undefined. Methods: We conducted a retrospective, multi-centre observational study including 77 mNSCLC patients who received pembrolizumab, pemetrexed and carboplatin CIT as first-line therapy for mNSCLC, between December 1, 2018 and January 1, 2020 in 3 academic referral centres in Europe and in the United States. We documented ATB exposure in the 30 days prior to CIT commencement (pATB) or concurrently (cATB) until CIT cessation. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from commencement of CIT, and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1). Results: We enrolled 77 patients, 41 of whom were female (n = 53%) with adenocarcinoma (n = 73, 95%), performance status (PS) 0-1 (n = 69, 90%) PD-L1 Tumour Proportion Score < 50 (n = 57, 74%). Median OS was 16.4 months (95%CI 8.4-24.4), median PFS was 6.7 months (95%CI 5.7-7.6). ORR was 48% including 1 complete (1%) and 36 partial responses (47%). Eleven patients (14%) received pATB, with penicillin/cephalosporins (p/c, n = 7, 63%) for <7 days (n = 10, 90%). Thirty-five patients (45%) received cATB with p/c (n = 11, 40%) for <7 days (n = 28, 80%). Most common indication for ATB was peri-procedure prophylaxis in pATB (n = 7, 63%) and suspected febrile neutropenia in cATB (n = 14, 40%). pATB (p = 0.004) but not cATB (p = 0.85) predicted for worse OS (19.6 vs 6.5 months, Hazard Ratio [HR] 2.9 95%CI 1.3-6.3). Neither pATB nor cATB predicted for PFS or ORR (p > 0.05). Multivariable analyses confirmed pATB (HR 2.3 95%CI 1.1-5.5, p = 0.05) to predict for OS independent of PD-L1 status, PS and cATB. pATB+/- groups were balanced with regards to age, gender, PS nor PD-L1 status (p > 0.05). Conclusions: Whilst cATB does not compromise outcome from CIT, this study reproduces the detrimental effects observed for pATB exposure in immunotherapy recipients. Mechanistic verification of the immune-biologic foundations underlying this association is urgently warranted.