Clinical Outcomes of Second-Line Chemotherapy in Patients with Previously Treated Advanced Thymic Carcinoma: A Retrospective Analysis of 191 Patients from the NEJ023 Study

Tateishi, Kazunari; Ko, Ryo; Shukuya, Takehito; Okuma, Yusuke; Watanabe, Satoshi; Kuyama, Shoichi; Murase, Kyoko; Tsukita, Yoko; Ashinuma, Hironori; Nagao, Taku; Uematsu, Kazutsugu; Nakao, Mika; Mori, Yoshiaki; Kaira, Kyoichi; Mouri, Atsuto; Miyabayashi, Takao; Sakashita, Hiroyuki; Matsumoto, Yōko; Tanigawa, Tomoyuki; Koizumi, Tomonobu; Morita, Satoshi; Kobayashi, Kunihiko; Nukiwa, Toshihiro; Takahashi, Kazuhisa

doi:10.1634/theoncologist.2019-0593

Cited by 15 publications

(23 citation statements)

References 31 publications

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“…The activity of sunitinib malate and Lenvatinib, two multi-targeted kinase inhibitors were tested in two phase 2 trials, in which 26 and 38% of patients with thymic carcinoma achieved a partial response, respectively ( 11 , 12 ). Anthracycline-based chemotherapy is recommended also by the National Comprehensive Cancer Network (NCCN) guidelines but the response rate is similar to that of other regimens and the problem of the best treatment in this setting remains open to debate ( 11 , 13 – 15 ). Immuno-oncology (IO) is changing the therapeutic landscape of thoracic malignancies, including TETs, although results are not still not conclusive ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

Pembrolizumab in a Patient With Heavily Pre-Treated Squamous Cell Thymic Carcinoma and Cardiac Impairment: A Case Report and Literature Review

et al. 2020

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Immunotherapy directed at the programmed cell death-1 receptor (PD-1) or its ligand PD-L1 has proven effective in solid malignancies such as melanoma, non-small cell lung cancer (NSCLC), urothelial cancer, renal cell carcinoma, and head and neck cancer. Compared with cytotoxic chemotherapy, radiotherapy, or molecular targeted agents, immunotherapy is an innovative strategy for treating malignancies, with durable clinical responses and manageable adverse events. Thymic carcinomas are extremely rare, constituting only 0.06% of all malignancies, are much more aggressive tumours than thymomas and have a worse prognosis. Nowadays, first line platinum-based chemotherapy for metastatic tumours are the cornerstone of treatment. However, the results of further therapeutic lines for metastatic or relapsed thymic carcinoma are unsatisfactory, with no regimen showing a consistent benefit. Moreover, the rarity of these tumours makes it difficult to carry out clinical trials. Herein we report a remarkable result of 1 year stable disease with good quality of life and no side effects obtained from the use of immunotherapy with pembrolizumab in a case of heavily pre-treated squamous cell thymic carcinoma and cardiac impairment. We also include a literature review of clinical trials on PD-1/PD-L1 inhibitors for the treatment of thymic epithelial cancers, taking a close look at cardiac toxicity.

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Section: Introductionmentioning

confidence: 99%

Pembrolizumab in a Patient With Heavily Pre-Treated Squamous Cell Thymic Carcinoma and Cardiac Impairment: A Case Report and Literature Review

et al. 2020

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“…When gemcitabine was used as the second-line chemotherapeutic agent, the response rate was 28.6%. 8 However, gemcitabine was only used as a second-line treatment for TC in the above studies, and there is no standard treatment after multiple lines of chemotherapy have been used. Because of its rarity, there are no randomized studies on the effects of chemotherapy in treatment of TC, and additional evidence is required to prove the efficacy of gemcitabine when used as a single agent in treatment of TC.…”

Section: Discussionmentioning

confidence: 99%

“…As most cases of TC are diagnosed at an advanced stage, chemotherapy is usually administered to slow the progress of the tumor. The efficacy of conventional chemotherapy in patients with advanced-stage or relapsing tumors is poor, 8 there are few published findings regarding the efficacy of secondline chemotherapy in patients with previously treated or advanced TC.…”

Section: Introductionmentioning

confidence: 99%

<p>The Effect and Safety of Anti-PD-1 Single/Combination Therapy in Refractory Thymic Carcinoma: A Case-Series Study</p>

Wei

Duan²,

Wang³

et al. 2020

CMAR

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Immunotherapy provided with checkpoint inhibitors such as the programmed cell death-1 (PD-1) receptor or its ligand-1 (PD-L1) protein has been shown to be effective for treating several types of cancer, and was recently approved for use in treating malignant melanoma, advanced non-small cell lung cancer (NSCLC), urothelial carcinoma, head and neck squamous cell carcinoma, liver cancer, and additional forms of cancer. However, there is little evidence concerning its effectiveness in treating thymic squamous cell carcinoma (TSCC). Here, we report two cases of refractory TSCC that were treated with PD-1 single/ combination therapy in a clinical setting. The patients exhibited variable responses to therapy without any serious adverse events. In summary, our findings show that immunotherapy provided with an immuno-checkpoint inhibitor in combination with chemotherapy/antiangiogenesis therapy can improve the treatment response of patients with refractory TSCC. Anti-PD-1 single/combination therapy may be used as a strategy for treating advanced refractory TC.

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“…Of several chemotherapeutic regimens, S-1, amrubicin, docetaxel, paclitaxel, gemcitabine, etoposide, sunitinib, everolimus, and lenvatinib have been reported as active drugs in previously treated patients with TC. Recently, Tateishi et al retrospectively analyzed the clinical outcomes of 191 patients with previously treated advanced TC [27]. As second-line chemotherapy in their study, platinum-based doublets, multidrug chemotherapy (e.g., ADOC), and monotherapy were observed in 57.6%, 13.6%, and 28.8%, respectively.…”

Section: Cytotoxic Agents As Salvage Chemotherapymentioning

confidence: 99%

Salvage Chemotherapy in Patients with Previously Treated Thymic Carcinoma

Kaira

Imai

Yamaguchi

et al. 2021

Cancers

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Thymic carcinoma is a rare neoplasm, and it is difficult to achieve complete remission with systemic chemotherapy. In advanced or recurrent thymic carcinoma, platinum-based chemotherapy is chosen as the first-line setting; however, it remains unclear which regimen is better to improve its outcome. It remains unknown whether salvage chemotherapy should be administered to patients with platinum-based chemotherapy-refractory thymic carcinoma. Currently, several clinical studies have investigated the efficacy of second-line settings for advanced thymic carcinoma. As cytotoxic agents, S-1, amrubicin, pemetrexed, docetaxel, paclitaxel, and gemcitabine have been reported as prospective phase II studies or retrospective studies. The overall response rates (ORRs) of S-1, amrubicin, and pemetrexed were 25–50%, 11–44.4%, and 9–10%, respectively. Molecular targeting drugs, such as sunitinib, everolimus, and lenvatinib, also provide clinical effectiveness with tolerability after the failure of platinum-based regimens. Based on the results of the prospective phase II study, the ORR, median progression-free survival, and median overall survival were 16.6% and 5.6 months, respectively, in everolimus, 26% and 7.2 months, respectively, in sunitinib, and 38% and 9.3 months, respectively, in lenvatinib. Although it is difficult to compare each study, lenvatinib appears to be better in increasing efficacy as a second-line setting. However, each study had a small sample size, which may have biased the results of their studies. Further investigation is warranted to elucidate the therapeutic significance of salvage chemotherapy in advanced thymic carcinoma in a large-scale study.

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Clinical Outcomes of Second-Line Chemotherapy in Patients with Previously Treated Advanced Thymic Carcinoma: A Retrospective Analysis of 191 Patients from the NEJ023 Study

Cited by 15 publications

References 31 publications

Pembrolizumab in a Patient With Heavily Pre-Treated Squamous Cell Thymic Carcinoma and Cardiac Impairment: A Case Report and Literature Review

Pembrolizumab in a Patient With Heavily Pre-Treated Squamous Cell Thymic Carcinoma and Cardiac Impairment: A Case Report and Literature Review

<p>The Effect and Safety of Anti-PD-1 Single/Combination Therapy in Refractory Thymic Carcinoma: A Case-Series Study</p>

Salvage Chemotherapy in Patients with Previously Treated Thymic Carcinoma

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