Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index

Buti, Sebastiano; Bersanelli, Melissa; Perrone, Fabiana; Tiseo, Marcello; Tucci, Marco; Adamo, Vincenzo; Stucci, Luigia Stefania; Russo, Alessandro; Tanda, Enrica T.; Spagnolo, Francesco; Rastelli, Francesca; Pergolesi, Federica; Santini, Daniele; Russano, Marco; Anesi, Cecilia; Giusti, Raffaele; Filetti, Marco; Marchetti, Paolo; Botticelli, Andrea; Gelibter, Alain; Occhipinti, Mario; Ferrari, Marco; Vitale, Maria Giuseppa; Nicolardi, Linda; Chiari, Rita; Rijavec, Erika; Nigro, Olga; Tuzi, Alessandro; Tursi, Michele De; Marino, Pietro Di; Conforti, Fabio; Queirolo, Paola; Bracarda, Sergio; Macrini, Serena; Gori, Stefania; Zoratto, Federica; Veltri, Enzo; Cocco, Barbara Di; Mallardo, Domenico; Vitale, Maria Grazia; Santoni, Matteo; Patruno, Leonardo; Porzio, Giampiero; Ficorella, Corrado; Pinato, David J.; Ascierto, Paolo A.; Cortellini, Alessio

doi:10.1016/j.ejca.2020.09.033

Cited by 92 publications

(111 citation statements)

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“…The aim of the present analysis was to describe clinicians’ attitudes towards single agent PD-1/PD-L1 checkpoint inhibitors administration and prescription during late stages of life, among a multicenter cohort of advanced cancer patients treated in clinical practice in Italy [ 8 – 15 ] (Additional file 1 , Table S1). This "ad-hoc" analysis has been performed on a cohort of patients already collected, after a follow-up update.…”

Section: Methodsmentioning

confidence: 99%

PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort

et al. 2021

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Background The favourable safety profile and the increasing confidence with immune checkpoint inhibitors (ICIs) might have boosted their prescription in frail patients with short life expectancies, who usually are not treated with standard chemotherapy. Methods The present analysis aims to describe clinicians’ attitudes towards ICIs administration during late stages of life within a multicenter cohort of advanced cancer patients treated with single agent PD-1/PD-L1 checkpoint inhibitors in Italy. Results Overall, 1149 patients with advanced cancer who received single agent PD-1/PD-L1 checkpoint inhibitors were screened. The final study population consisted of 567 deceased patients. 166 patients (29.3%) had received ICIs within 30 days of death; among them there was a significantly higher proportion of patients with ECOG-PS ≥ 2 (28.3% vs 11.5%, p < 0.0001) and with a higher burden of disease (69.3% vs 59.4%, p = 0.0266). In total, 35 patients (6.2%) started ICIs within 30 days of death; among them there was a higher proportion of patients with ECOG-PS ≥ 2 (45.7% vs 14.5%, p < 0.0001) and with a higher burden of disease (82.9% vs 60.9%, p = 0.0266). Primary tumors were significantly different across subgroups (p = 0.0172), with a higher prevalence of NSCLC patients (80% vs 60.9%) among those who started ICIs within 30 days of death. Lastly, 123 patients (21.7%) started ICIs within 3 months of death. Similarly, within this subgroup there was a higher proportion of patients with ECOG-PS ≥ 2 (29.3% vs 12.8%, p < 0.0001), with a higher burden of disease (74.0% vs 59.0%, p = 0.0025) and with NSCLC (74.0% vs 58.8%, p = 0.0236). Conclusion Our results confirmed a trend toward an increasing ICIs prescription in frail patients, during the late stages of life. Caution should be exercised when evaluating an ICI treatment for patients with a poor PS and a high burden of disease.

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Section: Methodsmentioning

confidence: 99%

PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort

et al. 2021

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“…16 Considering the hypothesized interaction between gut microbiota and ICI efficacy, several studies have examined the impact of PPI use on the survival of patients with cancer. [17][18][19][20][21][22][23][24][25] Due to the small sample size and the conflicting nature of the findings among the different studies, there has been no consensus on the significance of concomitant PPI use with regard to the clinical benefit of ICIs treatment. In the present study, we systematically reviewed the literature regarding the association of PPI use with ICI efficacy and conducted a meta-analysis to determine the effects of PPI use on outcomes in advanced cancer patients receiving ICI treatment.…”

Section: Introductionmentioning

confidence: 99%

Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer

et al. 2021

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Background: The present study aimed to evaluate the effects of concomitant proton pump inhibitor (PPI) use on immune checkpoint inhibitor (ICI) efficacy among advanced cancer patients. Methods and Materials: A systematic literature search of electronic database was performed to identify all potential reports. Then, meta-analyses were conducted to obtain pooled HRs with 95% CIs, which reveal the influence of PPI use on PFS and OS in patients receiving ICI treatment. Results: A total of 7 studies with 3,647 advanced cancer patients fulfilled the inclusion criteria. The impact of PPI use was then evaluated on 3,340 patients for PFS and 3,647 patients for OS. Concomitant PPI use has a detrimental effect on the efficacy of ICIs that PPI use increased the risk of progression by 28% (HR = 1.28, 95% CI 1.17-1.40; I2 = 31.3%, Q test P = .21) when compared to those not receiving PPIs. Similarly, the meta-analysis showed that PPI use was also associated with shorter OS of advanced cancer patients receiving ICIs that PPI use increased risk of death by 39% (HR = 1.39, 95% CI 1.26-1.54; I2 = 36.5%, Q test P = .16). Sensitivity analysis showed that the pooled HRs were constant after excluding one study at a time, and no significant publication biases were detected. Conclusion:The meta-analysis suggested that concomitant PPI use is significantly associated with low clinical benefit in ICI treatment, revealing a significantly reduced PFS and OS in advanced cancer patients receiving ICIs who are also exposed to PPI.

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“…PPI action is not only limit ed to the intestinal flora, but also that the tumor has been resistant to immunotherapy regenera te sensitive (34). During the preparation of our manuscript, we noticed that two meta-analyses w ere conducted last year to investigate the effect of PPI administration on the efficacy of cancer i mmunotherapy (35,36) (20,23,27) . And we did a more detailed subgroup analysis, and even reached some conclusions d ifferent from the previous two studies.…”

Section: Discussionmentioning

confidence: 99%

“…Firstly, we used the random effect model and found that PPI administration was significan tly related to the deterioration of OS(HR=1.31(1.11-1.52), P =0.001) and PFS(HR=1.21(0.93-1.3 4), P =0.22) in all patients receiving ICI, but PFS show no statistical significance may due to t he lack of relevant data in two studies (20,22). Sensitivity analysis and publication bias confirm ed the reliability of our results.…”

Section: Discussionmentioning

confidence: 99%

Concomitant of Proton Pump Inhibitors is Associated with Poor Clinical Outcomes in Patients Treated with Immune Checkpoint Inhibitors ：An Up-to-date Systematic Review and Meta-analysis

Mao

Tong

Yan

et al. 2021

Preprint

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Background: The emergence of immune checkpoint inhibitors has greatly changed the treatment outcome of advanced malignant tumors. The basic medication for patients with advanced solid tumors may affect the efficacy of immunotherapy. The use of proton pump inhibitors may change the acidic environment and inhibit intestinal flora, thereby affecting the efficacy of immunotherapy. To clarify the correlation between PPI administration and the prognosis of solid cancer patients treated with ICI, we conducted a meta-analysis.Method: Before February 12th, 2021, PubMed, Cochrane Library, Web of Science and EMBASE databases were used to search for eligible documents. The association of PPI administration with overall survival (OS) and progression-free survival (PFS), hazard ratio (HR) and 95% confidence interval (CI) were determined.Results: This study included 10 studies, a total of 4072 patients with solid cancer who received ICI treatment. Overall, the PPI administered with OS (HR=1.31 (1.11-1.52), P = 0.001) deteriorate significantly associated. In the subgroup analysis based on cancer type, PPI administration was associated with worsening of PFS in NSCLC, and better results of PFS in melanoma patients. In addition, between 30 days before the occurrence of ICI and 30 days after the occurrence of ICI, PPI administration may reduce the efficacy of ICI. Conclusion: Patients with solid cancer receiving ICI should use PPI with caution. However, only poor statistical results are observed on the OS, and further verification is still essential. This study was registered in PROSPERO with registration number CRD42021243707.

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Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index

Cited by 92 publications

References 38 publications

PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort

PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort

Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer

Concomitant of Proton Pump Inhibitors is Associated with Poor Clinical Outcomes in Patients Treated with Immune Checkpoint Inhibitors ：An Up-to-date Systematic Review and Meta-analysis

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