Prognostic and Predictive Biomarkers in the Era of Immunotherapy for Lung Cancer.

The therapeutic algorithm of lung cancer has recently been revolutionized by the emergence of immune checkpoint inhibitors. However, an objective and durable response rate remains low with those recent therapies and some patients even experience severe adverse events. Prognostic and predictive biomarkers are therefore needed in order to select patients who will respond. Nowadays, the only validated biomarker is the PD-L1 expression, but its predictive value remains imperfect, and it does not offer any certainty of a sustained response to treatment. With recent progresses in molecular biology, genome sequencing techniques, and the understanding of the immune microenvironment of the tumor and its host, new molecular features have been highlighted. There are evidence in favor of the positive predictive value of the tumor mutational burden, as an example. From the expression of molecular interactions within tumor cells to biomarkers circulating in peripheral blood, many markers have been identified as associated with the response to immunotherapy. In this review, we would like to summarize the latest knowledge about predictive and prognostic biomarkers of immune checkpoint inhibitors efficacy in order to go further in the field of precision immuno-oncology.

Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients? A meta-analysis.

Introduction: Gut microbiota can significantly affect the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. Recently, antibiotics were shown to decrease survival rate of patients treated by ICIs. Proton pump inhibitors (PPIs) can indeed modulate microbiota's diversity, therefore altering ICIs response. A meta-analysis was performed based on published data to verify this hypothesis. Methods: In this study, over 41 publications, exploring the impact of concomitant PPI treatment on outcomes of ICI-treated patients, were analyzed. Evaluated endpoints were overall survival (OS) and progression-free survival (PFS). Pooled hazard ratios (HRs) with a 95% confidence interval (CI) were reported in ICIs in PPI users versus non-PPI users. Subgroup analyses were performed to minimize the impact of study heterogeneity and to investigate the influence of PPI on the different groups of interest. There was no evidence of publication bias for OS and PFS analysis in subgroup analysis. Results: Forty-one studies were included in the meta-analysis, including a total of 20,042 patients. OS of patients receiving ICIs was negatively correlated in patients concomitantly treated with PPI (HR=1.37; 95%CI, 1.23-1.52). PFS of cancer patients receiving ICIs was also negatively correlated with PPI treatment (HR=1.28; 95%CI, 1.15-1.42). PPI and ICI use was associated with worst OS and PFS not only for non-small-cell lung cancer (NSCLC) or urothelial cancer patients but also for patients treated with anti PD-1 (OS) and anti PD-L1 (OS and PFS) immunotherapies when administered in non-first line and when PPI was received as baseline treatment or in 60 days before ICI initiation. PPI and ICI use also showed the worst OS and PFS for patients from Europe and Asia. Conclusion: This meta-analysis suggests that PPI treatment leads to significantly worse outcomes in advanced cancer patients treated by ICIs in terms of PFS and OS.

A case of hepatitis induced by herbal medicine in non-small cell lung cancer patient treated by a combination of immunotherapy and chemotherapy.

INTRODUCTION: Consumption of complementary and alternative medicine (CAM) is widely described in cancer patient. However, their composition is not clearly defined and the proofs of safety or effectiveness are quite low. We reported here the case of a CAM-induced hepatitis. CASE SUMMARY: A 33-years-old men with Non-Small Cell Lung Cancer and treated by combination of immunotherapy and chemotherapy developed hepatitis during 5 months. Viral and iatrogenic etiologies were excluded. MANAGEMENT AND OUTCOME: Medication reconciliation found concomitant utilisation of CAM. Some of the plants which composed CAM were found to be possible hepatotoxic. After discontinuation of this CAM, liver fonctions normalized. Close monitoring of liver function showed no other hepatitis. DISCUSSION: CAM induced hepatotoxicity was suspected. Medication reconciliation included CAM is needed in cancer patient to detect drug interactions and CAM side effects to improve cancer patient management.