Rapid Response to Pembrolizumab in a Chemo-Refractory Testicular Germ Cell Cancer with Microsatellite Instability-High

• Main Authors: Kawai K, Tawada A, Onozawa M, Inoue T, Sakurai H, Mori I, Takiguchi Y, Miyazaki J
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-09-01
• Series: OncoTargets and Therapy
• Subjects: pembrolizumab; testicular cancer; microsatellite instability
• Online Access: https://www.dovepress.com/rapid-response-to-pembrolizumab-in-a-chemo-refractory-testicular-germ--peer-reviewed-fulltext-article-OTT

Koji Kawai,1 Akinobu Tawada,2 Mizuki Onozawa,1 Takamitsu Inoue,1 Hiromichi Sakurai,1 Ichiro Mori,3 Yuichi Takiguchi,2 Jun Miyazaki1 1Department of Urology, International University of Health and Welfare Narita Hospital, Narita, Japan; 2Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan; 3Department of Pathology, International University of Health and Welfare Narita Hospital, Narita, JapanCorrespondence: Jun MiyazakiDepartment of Urology, International University of Health and Welfare Narita Hospital, 852 Hatakeda, Narita, Chiba, 286-0124, JapanTel [phone]Fax [phone]Email [e-mail]: Testicular germ cell tumor (TGCT) is highly chemo-sensitive cancer; however, there is no established treatment for TGCT relapsed after multiple chemotherapy. Although pembrolizumab showed durable stable disease in some patients, no reliable biomarker for predicting response is available. High microsatellite instability (MSI) is rare in chemo-naïve TGCT. We report a TGCT patient with a rapid response to pembrolizumab. A 34-year-old Japanese male diagnosed with advanced TGCT underwent PCR-based testing of the primary site; it did not reveal MSI. He relapsed after four chemotherapy regimens: bleomycin, etoposide and cisplatin; paclitaxel, ifosfamide and cisplatin; vinblastine, ifosfamide and cisplatin; and irinotecan+nedaplatin with a total of 20 treatment cycles. Chemotherapy was thus discontinued. Re-examination by a CT-guided needle biopsy for progressing retroperitoneal lymph node (RPLN) metastases showed MSI-high; pembrolizumab was initiated. After only two doses, the human chorionic gonadotropin level decreased from 6500 to < 1.0 IU/L. PET-CT showed shrinkage of the RPLN metastases with diminished metabolism. The patient is currently free from disease progression for 6 months from the start of pembrolizumab. This is the first report of refractory TGCT with MSI-high responding to pembrolizumab. We emphasize the utility of a metastatic-site biopsy to check the MSI status for refractory TGCT even when primary site is MSI-negative.Keywords: pembrolizumab, testicular cancer, microsatellite instability