A Phase II study suggests that apatinib therapy could be effective in treating thymic epithelial tumours after failure of platinum-based chemotherapy
Apatinib therapy seems to be an effective treatment option for patients with advanced thymic epithelial tumours who failed to achieve a satisfactory response after platinum-based chemotherapy. This was the conclusion of a small, Phase II trial by Chinese researchers.
Thymomas (T) and thymic carcinomas (TC) are tumours of the thymus gland and referred to as thymic epithelial tumours (TETs). These cancers are rare with an incidence of 1.7 per million per year in Europe. The mainstay of treatment for TETs is surgery and one retrospective analysis of outcomes after surgical resection found that the 5-year disease-free survival rate and overall survival rate was 59.7% and 66.2%, respectively. Despite the success of surgery, however, approximately 10-15% of resected tumours reoccur and, in cases of metastatic disease, one analysis has found that patients may benefit from a pemetrexed (platinum)-based chemotherapy regimen. Nevertheless, when chemotherapy fails, treatment options are limited. Some evidence suggests that in high risk TETs, there is increased expression of several vascular endothelial growth factors, which possess an angiogenic properties and have stimulant role in TETs. This finding indicates the potential value of angiogenesis inhibitors such as apatinib therapy as a treatment option in those failing to respond to chemotherapy. In fact, a study of a single patient with advanced thymic carcinoma found that apatinib therapy led to a progression-free survival of 6.3 months. Moreover, a second single patient study with advanced thymic squamous cell carcinoma also showed that apatinib therapy produced a 5-month overall response and a 10-month progression-free survival.
In light of these preliminary and potentially beneficial effects, the researchers decided to further investigate the value of this treatment in patients with TETs who had failed to respond to platinum-based chemotherapy. They performed an open-label, single-arm Phase II trial in adult patients with confirmed either T or TC and who had progressed after the failure of at least one line of systemic chemotherapy and had a life-expectancy of at least 3 months. Patients received apatinib therapy at a dose of 500mg once daily and a period of 28 days was considered as a treatment cycle. The primary endpoint was the confirmed objective response rate (OOR) and which they defined as the proportion of patients with the best response of complete response (CR) and partial response (PR). Secondary end points included progression-free survival (PFS) and overall survival (OS).
Apatinib and overall response
A total of 29 patients with a median age of 53 (68% male) were included although 4 patients were subsequently excluded. The remaining 25 patients received at least 1 apatinib cycle.
Overall, 1 patient achieved a complete response and 9 had a partial response, with an OOR of 40% (95% CI 21 – 61%). The median PFS was 9 months (95% CI 5.4 – 12.6) and the median OS was 24 months (95% CI 8.2 – 39.8).
The authors concluded that while this was the first prospective trial of apatinib therapy in patients with advanced TETs, the drug showed encouraging anti-tumour therapy and could serve as an alternative option for those with advanced disease.
Song Z et al. Apatinib in patients with recurrent or metastatic thymic epithelial tumor: a single-arm, multicenter, open-label, phase II trial BMC Med 2022