Treatment of CD30-Expressing Germ Cell Tumors and Sex Cord Stromal Tumors with Brentuximab Vedotin: Identification and Report of Seven Cases

Abstract

Background: Cytotoxic therapy for relapsed and refractory germ cell tumors or metastatic sex cord stromal tumors is rarely effective and is often accompanied by high adverse event rates. Expression of CD30 has been observed in testicular cancers, and patients with CD30-expressing embryonal carcinomas have worse progression-free survival and overall survival than those with CD30-negative tumors. The objective of this study (NCT01461538) was to characterize the antitumor activity of brentuximab vedotin in patients with CD30-expressing nonlymphomatous malignancies. Enrolled patients included seven patients with relapsed or refractory germ cell tumors or metastatic sex cord stromal tumors described in this case series.

Materials and methods: Forty patients with relapsed or refractory germ cell tumors, metastatic sex cord stromal tumors, or testicular tumors were screened for CD30 expression; 14 patients had tumors that expressed CD30. Seven patients with CD30-expressing testicular cancer were enrolled in the treatment study: five patients with germ cell tumors, one patient with a Leydig cell tumor, and one patient with a Sertoli cell tumor. Patients were treated with brentuximab vedotin at initial doses of 1.8 or 2.4 mg/kg every 3 weeks. Response assessments were performed at cycles 2 and 4 and every 4 cycles thereafter while the patient was receiving treatment.

Results: Two of seven patients achieved an objective response, including one durable complete response and one partial response at a single time point. Both responding patients had germ cell tumors. Treatment with brentuximab vedotin was generally well tolerated.

Conclusion: Treatment of relapsed or refractory germ cell tumors with brentuximab vedotin can induce durable responses with a manageable toxicity profile.

Implications for practice: This case series of seven patients with relapsed or refractory CD30-expressing germ cell tumors (GCTs) or sex cord stromal tumors demonstrates that brentuximab vedotin has activity against GCTs and is well tolerated in heavily pretreated patients with these aggressive tumor types. One patient achieved a complete response that has been durable for almost 4 years since the discontinuation of treatment with brentuximab vedotin. Therefore, brentuximab vedotin may be a valuable option for physicians who care for this difficult-to-treat patient population.

Keywords: CD30 antigen; Clinical trial; Germ cell tumor; Immunoconjugates; Sex cord stromal tumor.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

© AlphaMed Press 2017.

Figures

Figure 1.

Best responses in patients with testicular cancer treated with brentuximab vedotin. Swimmer's plot showing the best response and duration of response in all patients with testicular cancer treated with brentuximab vedotin. Solid bars represent time on treatment, and hatched bars represent time off treatment. Time of progression is noted by a black arrow, onset of partial responses by a brown diamond, onset of complete responses by a gray diamond, and time of death by a purple hexagon. The patient in Case 1 achieved a partial response at a single time point only. Abbreviations: CR, complete remission; PD, progressive disease; PR, partial response; SD, stable disease.

Figure 2.

Treatment with brentuximab vedotin induced a complete response in a patient (Case 4) with a germ cell tumor. Computed tomography scans over time of a right lung nodule (A), second right lung nodule (B), and mediastinal lymph node (C) in the patient in Case 4 who was treated with 1.8 mg/kg brentuximab vedotin. After cycle 2, the patient achieved a partial response that converted into a durable complete response after cycle 4.