Highlights
- •Immune checkpoint blockers strategy is feasible in pre-treated thymic carcinomas.
- •In this population, ICB achieve a RR of 18% and one-year OS of 67%.
- •Close monitoring of patients is strongly advised to detect severe immune-toxicity.
Abstract
Background
For patients with advanced thymic epithelial tumours (TET), there is no standard second-line
treatment after platinum-based chemotherapy. Although immune checkpoint blockers (ICB)
are a potential treatment strategy, their efficacy seems limited with an increased
risk of immune-related adverse events (ir-AEs), thus hampering their application in
daily clinical practice.
Methods
We performed a meta-analysis to better evaluate the existing evidence about the activity
and safety of ICB in the setting of unresectable or metastatic advanced TET previously
treated with platinum-based chemotherapy.
Results
Six phase I/II trials met the eligibility criteria including a total of 166 evaluable
patients (77% thymic carcinoma, 23% thymoma) evaluable for activity after being treated
with pembrolizumab, nivolumab, avelumab or atezolizumab. The overall response rate
to ICB was 18.4% (95% CI: 12.3–26.5), and the one-year progression-free survival rate
and one-year overall survival rate were 26.0% (95% CI: 19.6–34.6) and 66.9% (95% CI:
59.6–75.2%), respectively. The incidence of grade 3–5 ir-AEs was 26.4%, with 17.1%
in thymic carcinoma and 58.3% in thymoma.
Conclusions
Despite the absence of a robust demonstration of efficacy in the context of randomised
trials, our results suggest ICB as a potential strategy in patients with pretreated
TET, mainly among patients with thymic carcinoma. Close monitoring is strongly advised
to detect severe immune-toxicity.
Keywords
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References
- The 2021 WHO classification of tumors of the thymus and mediastinum: what is new in thymic epithelial, germ cell, and mesenchymal tumors?.J Thorac Oncol. 2022; 17: 200-213https://doi.org/10.1016/j.jtho.2021.10.010
- Trends in incidence and survival of patients with thymic epithelial tumor in a high-incidence Asian Country: analysis of the Korean Central Cancer Registry 1999 to 2017.J Thorac Oncol. 2022; 17: 827-837https://doi.org/10.1016/j.jtho.2022.02.001
- Autoimmune diseases in centrally reviewed thymic epithelial tumours (TET).Ann Oncol. 2020; 31: S1078https://doi.org/10.1016/j.annonc.2020.08.1442
- Imatinib mesylate in patients with WHO B3 thymomas and thymic carcinomas.J Thorac Oncol. 2009; 4: 1270-1273https://doi.org/10.1097/JTO.0b013e3181b6be57
- Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2015; 26: v40-v55https://doi.org/10.1093/annonc/mdv277
- Thymic epithelial tumors: from biology to treatment.Cancer Treat Rev. 2020; 86102014https://doi.org/10.1016/j.ctrv.2020.102014
- Systemic therapy in advanced thymic epithelial tumors: insights from the RYTHMIC prospective cohort.J Thorac Oncol. 2018; 13: 1762-1770https://doi.org/10.1016/j.jtho.2018.08.005
- Treatment strategies for thymic carcinoma in a real-life setting. Insights from the RYTHMIC network.Eur J Cancer. 2022; 162: 118-127https://doi.org/10.1016/j.ejca.2021.11.028
- The efficacy and safety of immunotherapy in thymic epithelial tumors: more effective, more risky: a systematic review.J Thorac Dis. 2021; 13: 5093-5103https://doi.org/10.21037/jtd-21-290
- Correlation between the expression of PD-L1 and clinicopathological features in patients with thymic epithelial tumors.BioMed Res Int. 2018; 20185830547https://doi.org/10.1155/2018/5830547
- Immune checkpoints in thymic epithelial tumors: challenges and opportunities.Immuno-Oncol Technol. 2019; 3: 8-14https://doi.org/10.1016/j.iotech.2019.09.002
- Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study.Lancet Oncol. 2018; 19: 347-355https://doi.org/10.1016/S1470-2045(18)30062-7
- Durable response in patients with thymic carcinoma treated with pembrolizumab after prolonged follow-up.J Thorac Oncol. 2021; 16: 483-485https://doi.org/10.1016/j.jtho.2020.11.003
- Pembrolizumab for patients with refractory or relapsed thymic epithelial tumor: an open-label phase II trial.J Clin Oncol. 2019; 37: 2162-2170https://doi.org/10.1200/JCO.2017.77.3184
- Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study.Eur J Cancer. 2019; 113: 78-86https://doi.org/10.1016/j.ejca.2019.03.012
- Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial.Ann Oncol. 2021; 32: S1342https://doi.org/10.1016/j.annonc.2021.08.2147
- Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma.J Immunother Cancer. 2019; 7: 269https://doi.org/10.1186/s40425-019-0723-9
- Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers.ESMO Open. 2022; 7100419https://doi.org/10.1016/j.esmoop.2022.100419
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS Med. 2009; 6e1000097https://doi.org/10.1371/journal.pmed.1000097
- IPDfromKM: reconstruct individual patient data from published Kaplan-Meier survival curves.BMC Med Res Methodol. 2021; 21: 111https://doi.org/10.1186/s12874-021-01308-8
- In meta-analyses of proportion studies, funnel plots were found to be an inaccurate method of assessing publication bias.J Clin Epidemiol. 2014; 67: 897-903https://doi.org/10.1016/j.jclinepi.2014.03.003
- Defining the most appropriate primary end point in phase 2 trials of immune checkpoint inhibitors for advanced solid cancers: a systematic review and meta-analysis.JAMA Oncol. 2018; 4: 522-528https://doi.org/10.1001/jamaoncol.2017.5236
- Continuous sunitinib schedule in advanced platinum refractory thymic epithelial neoplasms: a retrospective analysis from the ThYmic MalignanciEs (TYME) Italian collaborative group.Eur J Cancer. 2022; 174: 31-36https://doi.org/10.1016/j.ejca.2022.07.009
- Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial.Lancet Oncol. 2020; 21: 843-850https://doi.org/10.1016/S1470-2045(20)30162-5
- Lenvatinib for the treatment of thymic epithelial tumors (TETs): a real-life multicenter experience.J Clin Orthod. 2022; 40 (8585–8585)https://doi.org/10.1200/JCO.2022.40.16_suppl.8585
- Molecular predictors of response to pembrolizumab in thymic carcinoma.Cell Rep Med. 2021; 2100392https://doi.org/10.1016/j.xcrm.2021.100392
- The integrated genomic landscape of thymic epithelial tumors.Cancer Cell. 2018; 33: 244-258.e10https://doi.org/10.1016/j.ccell.2018.01.003
- Landscape of microsatellite instability across 39 cancer types.JCO Precis Oncol. 2017; 2017https://doi.org/10.1200/PO.17.00073
- Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors.Sci Rep. 2020; 10: 4064https://doi.org/10.1038/s41598-020-61053-8
- Immune checkpoint inhibitors therapies in patients with cancer and preexisting autoimmune diseases: a meta-analysis of observational studies.Autoimmun Rev. 2020; 19102687https://doi.org/10.1016/j.autrev.2020.102687
https://www.nccn.org/professionals/physician_gls/pdf/thymic.pdf n.d.
- Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC.Nat Rev Clin Oncol. 2021; 18: 625-644https://doi.org/10.1038/s41571-021-00520-1
- Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial.Lancet Oncol. 2022; (S1470-2045(22)00542-3. https://doi.org/10.1016/S1470-2045(22)00542-3)
Article info
Publication history
Published online: December 31, 2022
Accepted:
December 5,
2022
Received in revised form:
November 24,
2022
Received:
October 13,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.