Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: A Hoosier Cancer Research Network Study GU14-206

N. Adra, Lawrence Einhorn, S. K. Althouse, N. R. Ammakkanavar, D. Musapatika, Costantine Albany, D. Vaughn, Nasser Hanna

Research output: Contribution to journalArticle

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Abstract

Background: Despite remarkable results with salvage standard-dose or high-dose chemotherapy ~15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and methods: Single arm phase II trial investigating pembrolizumab 200mg i.v. Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at least one salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary end point was overall response rate using immune-related response criteria. Simon two-stage design with type I error 20% and power 80% was utilized. Results: Twelve male patients were enrolled. Median age was 38 years. All patients had nonseminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range 1-32, 760) and hCG 4 (range 0.6-37, 096). Six patients had late relapse (>2 years). Median number of previous chemotherapy regimens was 3. Six patients received prior high-dose chemotherapy. Two patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range 1-8). There were six grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. Two patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining. Conclusion: This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT.

Original languageEnglish (US)
Article numbermdx680
Pages (from-to)209-214
Number of pages6
JournalAnnals of Oncology
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Germ Cell and Embryonal Neoplasms
Platinum
Research
Neoplasms
Drug Therapy
Ligands
pembrolizumab
Staining and Labeling
Mediastinum
Immunotherapy
Cisplatin
Disease Progression
Testis
Arm
Recurrence

Keywords

  • Checkpoint inhibitors
  • Germ-cell tumor
  • Immunotherapy
  • Pembrolizumab
  • Testicular cancer

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors : A Hoosier Cancer Research Network Study GU14-206. / Adra, N.; Einhorn, Lawrence; Althouse, S. K.; Ammakkanavar, N. R.; Musapatika, D.; Albany, Costantine; Vaughn, D.; Hanna, Nasser.

In: Annals of Oncology, Vol. 29, No. 1, mdx680, 01.01.2018, p. 209-214.

Research output: Contribution to journalArticle

Adra, N. ; Einhorn, Lawrence ; Althouse, S. K. ; Ammakkanavar, N. R. ; Musapatika, D. ; Albany, Costantine ; Vaughn, D. ; Hanna, Nasser. / Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors : A Hoosier Cancer Research Network Study GU14-206. In: Annals of Oncology. 2018 ; Vol. 29, No. 1. pp. 209-214.
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abstract = "Background: Despite remarkable results with salvage standard-dose or high-dose chemotherapy ~15{\%} of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and methods: Single arm phase II trial investigating pembrolizumab 200mg i.v. Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at least one salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary end point was overall response rate using immune-related response criteria. Simon two-stage design with type I error 20{\%} and power 80{\%} was utilized. Results: Twelve male patients were enrolled. Median age was 38 years. All patients had nonseminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range 1-32, 760) and hCG 4 (range 0.6-37, 096). Six patients had late relapse (>2 years). Median number of previous chemotherapy regimens was 3. Six patients received prior high-dose chemotherapy. Two patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range 1-8). There were six grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. Two patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining. Conclusion: This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT.",
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AU - Ammakkanavar, N. R.

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AB - Background: Despite remarkable results with salvage standard-dose or high-dose chemotherapy ~15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and methods: Single arm phase II trial investigating pembrolizumab 200mg i.v. Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at least one salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary end point was overall response rate using immune-related response criteria. Simon two-stage design with type I error 20% and power 80% was utilized. Results: Twelve male patients were enrolled. Median age was 38 years. All patients had nonseminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range 1-32, 760) and hCG 4 (range 0.6-37, 096). Six patients had late relapse (>2 years). Median number of previous chemotherapy regimens was 3. Six patients received prior high-dose chemotherapy. Two patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range 1-8). There were six grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. Two patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining. Conclusion: This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT.

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