Patients with rare thymic carcinoma and progressive disease following treatment with platinum-based chemotherapy may have a new treatment option with lenvatinib, according to findings from a phase II study reported at the ESMO Congress 2019 in Barcelona, Spain.
Currently, the standard treatment for thymic carcinoma is platinum-based chemotherapy, but no standard treatment is in place for patients who experience disease progression following this therapy.
Reports from several trials suggest that multi-targeted inhibitors primarily targeting the vascular endothelial growth factor receptor (VEGFR) have anti-tumour activity in several cancer types, prompting Shoichi Itoh, Department of Thoracic Oncology, Hyogo Cancer Centre, Hyogo, Japan and a team of Japanese researchers to investigate the efficacy of lenvatinib, a novel multi-targeted inhibitor of VEGFR and key elements of other pathways in thymic carcinoma.
They conducted an open-label, single-arm, multi-centre phase II REMORA trial (JMA-IIA00285) to assess the efficacy and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma. Eligible patients had histologically confirmed thymic carcinoma, disease progression after at least one prior platinum-based chemotherapy, ECOG performance status of 0 or 1, measurable lesions, and adequate organ function. A total of 42 patients were enrolled from 8 institutions across Japan who were treated with 24 mg of oral lenvatinib once daily until progression or unacceptable toxicities.
The primary endpoint was objective response rate (ORR) by independent radiological review. The study utilised a SWOG two-stage design, which provided 80% power with a sample size of 40, one-sided alpha error of 5%, a threshold ORR of 10% and an expected ORR of 25%.
Lenvatinib treatment yielded partial responses and stable disease
With median follow-up of 15.5 months, interquartile range (IQR) 13.1-17.5, the ORR was 38.1% (90 % confidence interval [CI], 25.6-52.0), thus meeting the primary endpoint. The best overall response comprised 16 partial responses and 24 patients with stable disease.
Primary endpoint (Objective Response).
© Shoichi Itoh.
Frequently reported treatment-related adverse events of any grade included hypertension, diarrhoea, hand-foot syndrome, proteinuria, hypothyroidism, and decreased platelet count.
Conclusions
The investigators concluded that the efficacy and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma was confirmed.
The results of this study suggest that lenvatinib could become one of the standard treatment options in patients with advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy.
Disclosure
This trial was sponsored by the Centre for Clinical trials, the Japan Medical Association, and Eisai.
Reference
1844O – Itoh S, Satouchi M, Sato J, et al. Durable anti-tumor activity of the multi-targeted inhibitor lenvatinib in patients with advanced or metastatic thymic carcinoma; Preliminary results from a multicenter phase II (REMORA) trial.