The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial, Germ Cell, and Mesenchymal Tumors?

http://www.jto.org/article/S1556086421032585/pdf

Solid cancers comprise a large number of new cases and deaths from cancer each year globally. There are a number of strategies for addressing tumors raised from solid organs including surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, combinational therapy, and stem cell and extracellular vesicle (EV) therapy. Surgery, radiotherapy, and chemotherapy are the dominant cures, but are not always effective, in which even in a localized tumor there is a possibility of tumor relapse after surgical resection. Over half of the cancer patients will receive radiotherapy as a part of their therapeutic schedule. Radiotherapy can cause an abscopal response for boosting the activity of the immune system outside the local field of radiation, but it may also cause an unwanted bystander effect, predisposing nonradiated cells into carcinogenesis. In the context of immunotherapy, immune checkpoint inhibition is known as the standard-of-care, but the major concern is in regard with cold cancers that show low responses to such therapy. Stem-cell therapy can be used to send prodrugs toward the tumor area; this strategy, however, has its own predicaments, such as unwanted attraction toward the other sites including healthy tissues and its instability. A substitute to such therapy and quite a novel strategy is to use EVs, by virtue of their stability and potential to cross biological barriers and long-term storage of contents. Combination therapy is the current focus. Despite advances in the field, there are still unmet concerns in the area of effective cancer therapy, raising challenges and opportunities for future investigations.

The current knowledge concerning solid cancer and therapy.

http://www.jto.org/article/S1556086422000909/pdf

Thymic Carcinomas - A Concise Multidisciplinary Update on Recent Developments from the Thymic Carcinoma Working Group of the International Thymic Malignancy Interest Group.

Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review.

Summary Background Thymic carcinoma is a rare malignant disease and standard treatment for advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy has not been established. Lenvatinib is a novel multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The aim of this trial was to assess the activity and safety of lenvatinib as a second-line treatment in thymic carcinoma. Methods This single-arm, phase 2 trial done in eight institutions in Japan (five cancer centres, two medical university hospitals, and one public hospital) enrolled patients with pathologically confirmed unresectable advanced or metastatic thymic carcinoma that progressed following at least one platinum-based chemotherapy. Key inclusion criteria were age 20 years or older, at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 24 mg of lenvatinib orally once daily in 4-week cycles until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate evaluated at the data cutoff date (Feb 22, 2019), by independent central review in the intention-to-treat population. This trial is registered on JMACCT, JMA-IIA00285, and on UMIN-CTR, UMIN000026777. Findings Between April 21, 2017, and Feb 22, 2018, 42 patients were enrolled and all patients were included in the activity and safety analysis. The median follow-up period was 15·5 months (IQR 13·1–17·5). The objective response rate was 38% (90% CI 25·6–52·0, p Interpretation The activity and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma was confirmed. These results suggest that lenvatinib could become a standard treatment option for patients with previously treated advanced or metastatic thymic carcinoma. Funding Center for Clinical Trials, Japan Medical Association.

Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial.

The aim of this study was to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC were eligible. In the phase I dose-escalation cohort (3 + 3 design), patients received nab-paclitaxel (80 or 100 mg/m2 given intravenously on days 1, 8 and 15) plus cisplatin (60 or 75 mg/m2 given intravenously on day 1) every 4 weeks. The maximum tolerated dose was not reached. Nab-paclitaxel (100 mg/m2 given intravenously on days 1, 8 and 15) plus cisplatin (75 mg/m2 given intravenously on day 1) every 4 weeks was selected for the phase II cohort. The primary endpoint was the objective response rate (ORR). Twenty-three patients (phase I, n = 6; phase II, n = 17) were enrolled, and 22 patients were eligible. The median age was 67.5 years (range 37–75), 90.9% were males, 45.5% had adenocarcinoma and 81.8% had stage IV disease. The ORR was 59.1% (90% confidence interval (CI); 41.8–74.4), and the disease control rate was 86.4% (95% CI; 66.7–95.3). The median progression-free survival was 5.1 months (95% CI; 4.0–6.7), and the median overall survival was 24.2 months (95% CI; 8.4 months to not estimable). The common grade ≥ 3 adverse events were neutropenia (31.8%), leukopenia (27.3%), lung infection (18.2%) and hyponatremia (18.2%). There was one instance of grade 2 interstitial pneumonia and no treatment-related death. Nab-paclitaxel plus cisplatin was well tolerated and associated with encouraging response outcomes in chemotherapy-naive patients with advanced NSCLC. Further investigation is warranted. UMIN Clinical Trials Registry: UMIN000011776; Date of registration: 17 September 2013; Date of enrolment of the first participant to the trial: 23 January 2014.

/pdf/a-phase-i-ii-study-of-weekly-nab-paclitaxel-plus-cisplatin-3r4i0luv83.pdf

A phase I/II study of weekly nab-paclitaxel plus cisplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer

Background Carboplatin plus nanoparticle albumin-bound paclitaxel (nab-PTX) is one of the available first-line treatments for non-small cell lung cancer (NSCLC) patients. However, the efficacy of carboplatin plus nab-PTX as second-line, remains unknown. We examined the efficacy of carboplatin plus nab-PTX after cisplatin plus pemetrexed in non-squamous NSCLC patients. Methods We retrospectively reviewed advanced non-squamous NSCLC patients who received carboplatin plus nab-PTX as a second-line chemotherapy regimen after cisplatin plus pemetrexed in our hospital between March 2013 and December 2017. We assessed clinical characteristics, efficacy, and toxicities. Results Forty-four patients were recruited. The overall response rate (ORR) was 29% and the disease control rate (DCR), 69%. The median progression-free survival (mPFS) was 3.7 months (95% CI: 2.4–5.5 months) and the median overall survival, 16.6 months (95% CI:8.8–19.5 months). We assessed the ORR and mPFS using the best overall response in the prior regimen. The ORR and mPFS were better in the PD group (ORR; 44% and mPFS: 5.6 months). Conclusions Carboplatin plus nab-PTX after cisplatin plus pemetrexed in non-squamous NSCLC patients is a treatment option. There were several cases where cisplatin plus pemetrexed was not effective, but Carboplatin plus nab-PTX was.

The efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel after cisplatin plus pemetrexed in non-squamous non-small-cell lung cancer patients.

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Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial.

A phase I/II study of weekly nab-paclitaxel plus cisplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer

The efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel after cisplatin plus pemetrexed in non-squamous non-small-cell lung cancer patients.