Phase II study of avelumab in multiple relapsed/refractory germ cell cancer
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Background Germ cell tumors (GCTs) are highly curable diseases; however, not all patients can be cured. Patients in their second relapse have especially poor prognoses. PD-L1 expression is significantly higher in GCTs than in normal testicular tissue, and high PD-L1 expression is associated with a poor prognosis. This study aimed to determine the efficacy and safety of avelumab, a PD-L1 inhibitor, in patients with GCTs. Methods In this phase 2 study, patients with multiple relapsed and/or refractory GCTs were treated with avelumab at a dose of 10 mg/kg administered biweekly until progression or unacceptable toxicity. The primary endpoint was 12-week progression-free survival (PFS). Fifteen evaluable patients had to be enrolled in the first cohort, and if <8 of 15 patients had 12-week PFS, the study was to be terminated. Here, we report the results of the first stage of the trial. Results From November 2017 to January 2018, 8 patients with a median age of 29 years (range, 22 to 52 months) were enrolled. Patients were pretreated with a median of 5 (range, 1 to 6) previous lines of platinum-based therapies; 5 tumors (62.5%) were absolutely refractory to cisplatin, and 5 patients (62.5%) had visceral nonpulmonary metastases. At a median follow-up period of 2.6 months (range, 0.3 to 14.4), all the patients experienced disease progression, and 7 patients (87.5%) died. The twelve-week PFS was 0%, median PFS was 0.9 months (95% CI 0.5–1.9), and median OS was 2.7 months (95% CI 1.0–3.3). Avelumab was well tolerated, and no severe adverse events were observed. Conclusions This study failed to achieve its primary endpoint. Our data suggest a lack of avelumab efficacy in unselected multiple relapsed/refractory GCTs.
KeywordsAvelumab Germ cell tumors Immune checkpoint inhibitors PD-L1 expression Refractory germ cell tumors
We would like to acknowledge Dr. De Angelis V, Dr. Miskovska V and Dr. Andrasina I for their collaboration and Krieschova A, Jancikova A, Turnova S, Gombarova V, Polakova H and Pekova Z for providing administrative support.
M-M, MC-C, U-DG and J-M participated in the conception and design of this study. D-S and M-R participated in data validation, and K-R, J-O, P-P, and Z-SM acquired, analyzed and interpreted the data. M-M drafted the article, and all the authors reviewed it critically for its important intellectual content.
This work was supported by the Scientific Grant Agency of the Ministry of Education (Projects No. VEGA 1/0174/19 and VEGA 1/0043/18).
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
All the procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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