Hypertransaminasemia in Cancer Patients Receiving Immunotherapy and Immune-based Combinations: the MOUSEION-05 Study

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2023 Jan 25

PMID 36695827

Authors

Alessandro Rizzo

Veronica Mollica

Valentina Tateo

Elisa Tassinari

Andrea Marchetti

Matteo Rosellini

Raffaele De Luca

Matteo Santoni

Francesco Massari

Affiliations

Soon will be listed here.

Abstract

Background: The antitumor efficacy of immune checkpoint inhibitors (ICIs) has increasingly emerged during the last few years. However, there is a need to identify the safety profile of these agents more comprehensively, including liver toxicity.

Materials And Methods: Herein, we performed a meta-analysis to assess the risk of all-grade and grade 3-4 hypertransaminasemia in cancer patients receiving ICIs-as monotherapy or in combination with other anticancer agents. All the relevant trials were retrieved through EMBASE, Cochrane Library, and PubMed/Medline databases; eligible studies were selected according to PRISMA statement. The pooled relative risk (RR) and 95% confidence interval (CI) were extracted.

Results: Fifty-nine studies were included. The pooled RRs for all-grade AST and ALT increase were 1.45 (95% CI 1.26-1.67) (Supplementary Fig. 3) and 1.51 (95% CI 1.29-1.77) in patients receiving ICIs monotherapy and immune-based combinations compared to control treatment, respectively. The pooled RRs for grade 3-4 AST and ALT increase were 2.16 (95% CI 1.77-2.64) and 2.3 (95% CI 1.91-2.77).

Conclusions: According to our results, ICIs monotherapy and immune-based combinations were associated with higher risk of all-grade and grade 3-4 hypertransaminasemia. Monitoring liver function should be recommended in cancer patients treated with ICIs monotherapy or immune-based combination, and in case of underlying liver disease, a careful risk-benefit assessment appears as a mandatory need.

Citing Articles

First-Line Treatment of Icaritin and Thalidomide in a Patient With Hepatocellular Carcinoma With PR: A Case Report.

Jin Z, Zhou F, Wang Z, Li H Cancer Rep (Hoboken). 2025; 8(3):e70136.

PMID: 40035422 PMC: 11877328. DOI: 10.1002/cnr2.70136.

Preclinical study of inetetamab combined with atezolizumab to synergistically inhibit HER2 and PD-L1 in the treatment of ovarian cancer.

Ying F, Zhou X, Chen M, Huang L, Gao L, Zhao Q Mol Ther Oncol. 2025; 33(1):200938.

PMID: 40034965 PMC: 11874541. DOI: 10.1016/j.omton.2025.200938.

Predictive factors of chemotherapy‑induced nausea and vomiting in elderly patients with gynecological cancer undergoing paclitaxel and carboplatin therapy: A retrospective study.

Yao F, He L, Sun X Oncol Lett. 2025; 29(4):167.

PMID: 39958929 PMC: 11826289. DOI: 10.3892/ol.2025.14913.

Efficacy and safety of different drugs in patients with HER2-positive gastric cancer: network meta-analysis.

Zhang J, Yuan C, Ma X Syst Rev. 2025; 14(1):40.

PMID: 39930467 PMC: 11808970. DOI: 10.1186/s13643-025-02777-4.

Unlocking the potential of : A breakthrough in liver cancer treatment Wnt/β-catenin pathway modulation.

Benmediouni F World J Gastroenterol. 2025; 31(4):99397.

PMID: 39877712 PMC: 11718646. DOI: 10.3748/wjg.v31.i4.99397.

References

Socinski M, Jotte R, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N . Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018; 378(24):2288-2301. DOI: 10.1056/NEJMoa1716948. View

Reckamp K, Redman M, Dragnev K, Minichiello K, Villaruz L, Faller B . Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non-Small-Cell Lung Cancer Previously Treated With Immunotherapy-Lung-MAP S1800A. J Clin Oncol. 2022; 40(21):2295-2306. PMC: 9287284. DOI: 10.1200/JCO.22.00912. View

Reardon D, Brandes A, Omuro A, Mulholland P, Lim M, Wick A . Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020; 6(7):1003-1010. PMC: 7243167. DOI: 10.1001/jamaoncol.2020.1024. View

Tian Y, Abu-Sbeih H, Wang Y . Immune Checkpoint Inhibitors-Induced Hepatitis. Adv Exp Med Biol. 2018; 995:159-164. DOI: 10.1007/978-3-030-02505-2_8. View

Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F . Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol. 2015; 27(4):559-74. DOI: 10.1093/annonc/mdv623. View

Pujade-Lauraine E, Fujiwara K, Ledermann J, Oza A, Kristeleit R, Ray-Coquard I . Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol. 2021; 22(7):1034-1046. DOI: 10.1016/S1470-2045(21)00216-3. View

Albiges L, Powles T, Staehler M, Bensalah K, Giles R, Hora M . Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma. Eur Urol. 2019; 76(2):151-156. DOI: 10.1016/j.eururo.2019.05.022. View

Barlesi F, Vansteenkiste J, Spigel D, Ishii H, Garassino M, de Marinis F . Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. Lancet Oncol. 2018; 19(11):1468-1479. DOI: 10.1016/S1470-2045(18)30673-9. View

Choueiri T, Powles T, Burotto M, Escudier B, Bourlon M, Zurawski B . Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021; 384(9):829-841. PMC: 8436591. DOI: 10.1056/NEJMoa2026982. View

10.

Powles T, van der Heijden M, Castellano D, Galsky M, Loriot Y, Petrylak D . Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2020; 21(12):1574-1588. DOI: 10.1016/S1470-2045(20)30541-6. View

11.

Rosellini M, Marchetti A, Mollica V, Rizzo A, Santoni M, Massari F . Prognostic and predictive biomarkers for immunotherapy in advanced renal cell carcinoma. Nat Rev Urol. 2022; 20(3):133-157. DOI: 10.1038/s41585-022-00676-0. View

12.

Schmid P, Adams S, Rugo H, Schneeweiss A, Barrios C, Iwata H . Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018; 379(22):2108-2121. DOI: 10.1056/NEJMoa1809615. View

13.

Santoni M, Rizzo A, Mollica V, Matrana M, Rosellini M, Faloppi L . The impact of gender on The efficacy of immune checkpoint inhibitors in cancer patients: The MOUSEION-01 study. Crit Rev Oncol Hematol. 2022; 170:103596. DOI: 10.1016/j.critrevonc.2022.103596. View

14.

Diaz Jr L, Shiu K, Kim T, Jensen B, Jensen L, Punt C . Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022; 23(5):659-670. PMC: 9533375. DOI: 10.1016/S1470-2045(22)00197-8. View

15.

Motzer R, Alekseev B, Rha S, Porta C, Eto M, Powles T . Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021; 384(14):1289-1300. DOI: 10.1056/NEJMoa2035716. View

16.

Chung H, Kang Y, Chen Z, Bai Y, Wan Ishak W, Shim B . Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. Cancer. 2021; 128(5):995-1003. PMC: 9299889. DOI: 10.1002/cncr.34019. View

17.

Viscardi G, Tralongo A, Massari F, Lambertini M, Mollica V, Rizzo A . Comparative assessment of early mortality risk upon immune checkpoint inhibitors alone or in combination with other agents across solid malignancies: a systematic review and meta-analysis. Eur J Cancer. 2022; 177:175-185. DOI: 10.1016/j.ejca.2022.09.031. View

18.

Powles T, Duran I, van der Heijden M, Loriot Y, Vogelzang N, De Giorgi U . Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2017; 391(10122):748-757. DOI: 10.1016/S0140-6736(17)33297-X. View

19.

Herbst R, Baas P, Kim D, Felip E, Perez-Gracia J, Han J . Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015; 387(10027):1540-1550. DOI: 10.1016/S0140-6736(15)01281-7. View

20.

Felip E, Altorki N, Zhou C, Csoszi T, Vynnychenko I, Goloborodko O . Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021; 398(10308):1344-1357. DOI: 10.1016/S0140-6736(21)02098-5. View