Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy

Cortellini, Alessio; Ricciuti, Biagio; Facchinetti, Francesco; Alessi, Joao; Venkatraman, Deepti; Dall’Olio, Filippo Gustavo; Cravero, Paola; Vaz, Victor R.; Ottaviani, Diego; Majem, Margarita; Piedra, A.; Sullivan, Ivana; Lee, K.A.; Lamberti, Giuseppe; Hussain, Nadiya; Clark, James J.; Bolina, Anita; Barba, Andrés; Benítez, José Carlos; Gorría, Teresa; Mezquita, Laura; Hoton, Delphine; Nana, Frank Aboubakar; Besse, Benjamin; Awad, Mark M.; Pinato, David J.

doi:10.1016/j.annonc.2021.08.1744

Cited by 48 publications

(37 citation statements)

References 19 publications

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“…For instance, our group recently showed that a previous antibiotic therapy does not impair treatment outcomes in patients with NSCLC treated with chemoimmunotherapy combinations, as reported with single-agent ICI instead. 9 10 The absence of a BMI-dependent effect on clinical outcome mirrors these findings and highlights how the host determinants of benefit from ICI might have different roles depending on the specific treatment modality. In the context of single-agent ICI regimens, obesity has been interpreted as a driver of reduced responsivity of peripheral T cells, due to the a dysfunctional PD-1/PD-L1-driven immune exhaustion, which could explain the magnified effect of PD-1/PD-L1 inhibitors in restoring T-cell activity in obese individuals.…”

Section: Discussionmentioning

confidence: 66%

Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations

Cortellini

Ricciuti

Vaz

et al. 2022

J Immunother Cancer

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IntroductionIt has been recognized that increasing body mass index (BMI) is associated with improved outcome from immune checkpoint inhibitors (ICIs) in patients with various malignancies including non-small cell lung cancer (NSCLC). However, it is unclear whether baseline BMI may influence outcomes from first-line chemoimmunotherapy combinations.MethodsIn this international multicenter study, we evaluated the association between baseline BMI, progression-free survival (PFS) and overall survival (OS) in a cohort of patients with stage IV NSCLC consecutively treated with first-line chemoimmunotherapy combinations. BMI was categorized according to WHO criteria.ResultsAmong the 853 included patients, 5.3% were underweight; 46.4% were of normal weight; 33.8% were overweight; and 14.5% were obese. Overweight and obese patients were more likely aged ≥70 years (p=0.00085), never smokers (p<0.0001), with better baseline Eastern Cooperative Oncology Group—Performance Status (p=0.0127), and had lower prevalence of central nervous system (p=0.0002) and liver metastases (p=0.0395). Univariable analyses showed a significant difference in the median OS across underweight (15.5 months), normal weight (14.6 months), overweight (20.9 months), and obese (16.8 months) patients (log-rank: p=0.045, log rank test for trend: p=0.131), while no difference was found with respect to the median PFS (log-rank for trend: p=0.510). Neither OS nor PFS was significantly associated with baseline BMI on multivariable analysis.ConclusionsIn contrast to what was observed in the context of chemotherapy-free ICI-based regimens, baseline BMI does not affect clinical outcomes from chemoimmunotherapy combinations in patients with advanced NSCLC.

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Section: Discussionmentioning

confidence: 66%

Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations

Cortellini

Ricciuti

Vaz

et al. 2022

J Immunother Cancer

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“…Antibiotic administration within 30 days prior to the commencement of tumor immunotherapy significantly shortens PFS and OS [ 106 ]. However, recent studies suggest that antibiotic use does not affect the efficacy of first-line chemotherapy combined with ICI in patients with advanced NSCLC [ 107 ]. Therefore, whether the use of antibiotics affects the antitumor efficacy of ICI still needs more research.…”

Section: Host-related Biomarkersmentioning

confidence: 99%

The key to immunotherapy: how to choose better therapeutic biomarkers for patients with non-small cell lung cancer

Pan

Zeng

et al. 2022

Biomark Res

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Immunotherapy has become the standard of care for non-small cell lung cancer (NSCLC), either in combination or monotherapy. However, there are still some patients who cannot benefit from it. Immunization strategies for NSCLC are based on the expression of PD-L1 on tumor cells and TMB, and although these indicators have a certain predictive effect, their predictive performance is not good. Therefore, clinicians must make adjustments to recognize markers. This is a review article that summarized immunotherapeutic biomarkers according to the “seed-soil-environment”, generalizes primary resistance to immunotherapy, and summarizes the integration of markers.

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“…On the basis of the best overall response, patients with complete or partial response were considered responders, while others with stable or progressive disease were considered non-responders. The progression-free survival (PFS) and OS were defined as the interval from treatment initiation to the date of clinical progression or death, and to the date of death from any cause, respectively ( 31 ). Survival status was obtained through medical records or telephone follow-up every 2 cycles of chemo-immunotherapy.…”

Section: Methodsmentioning

confidence: 99%

High farnesoid X receptor expression predicts favorable clinical outcomes in PD‑L1^low/negative non‑small cell lung cancer patients receiving anti‑PD‑1‑based chemo‑immunotherapy

Wang

Shang

et al. 2022

Int J Oncol

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Anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-directed immunotherapy has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). However, predictive biomarkers are still lacking, particularly in identifying PD-L1 low/negative patients who will benefit from immunotherapy. It was previously reported that farnesoid X receptor (FXR) downregulated PD-L1 expression in NSCLC, and that FXR high PD-L1 low mouse Lewis lung carcinoma tumors showed an increased susceptibility to PD-1 blockade compared with mock tumors. At present, whether the FXR high PD-L1 low phenotype predicts clinical response to immunotherapy in patients with NSCLC remains unclear. Herein, a retrospective study was conducted to examine the expression levels of FXR, PD-L1 and CD8 + T cells by immunohistochemistry in a cohort of 149 patients with NSCLC receiving anti-PD-1-based chemo-immunotherapy. The results revealed that high FXR and PD-L1 expression levels were associated with higher objective response rates (ORR) in all patients. High PD-L1 expression also indicated superior progression-free survival (PFS). Interestingly, an inverse correlation was identified between FXR and PD-L1 expression in specimens with NSCLC. Subgroup analysis revealed that high FXR expression was associated with a higher ORR, as well as longer PFS and overall survival (OS) in PD-L1 low patients. Cox multivariate analysis revealed that high FXR expression was an independent predictor for PFS and OS in PD-L1 low patients. Tumor microenvironment evaluation revealed a statistically significant decrease of infiltrating CD8 + T cells in FXR high specimens with NSCLC. Overall, the present study proposed an FXR high PD-L1 low signature as a candidate predictor of response to anti-PD-1-based chemo-immunotherapy in PD-L1 low/negative patients with NSCLC, providing evidence that could be used to broaden the patients benefitting from immunotherapy.

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Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy

Cited by 48 publications

References 19 publications

Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations

Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations

The key to immunotherapy: how to choose better therapeutic biomarkers for patients with non-small cell lung cancer

High farnesoid X receptor expression predicts favorable clinical outcomes in PD‑L1^low/negative non‑small cell lung cancer patients receiving anti‑PD‑1‑based chemo‑immunotherapy

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Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy

Cited by 48 publications

References 19 publications

Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations

Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations

The key to immunotherapy: how to choose better therapeutic biomarkers for patients with non-small cell lung cancer

High farnesoid X receptor expression predicts favorable clinical outcomes in PD‑L1low/negative non‑small cell lung cancer patients receiving anti‑PD‑1‑based chemo‑immunotherapy

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High farnesoid X receptor expression predicts favorable clinical outcomes in PD‑L1^low/negative non‑small cell lung cancer patients receiving anti‑PD‑1‑based chemo‑immunotherapy