Immunotherapy in Testicular Cancer: Were We Are and ...
Transcript of Immunotherapy in Testicular Cancer: Were We Are and ...
André P. Fay, MD, PhD
Professor of Medicine - PUCRS School of MedicineChief, Medical Oncology Department at HSL – PUCRS/Grupo Oncoclínicas
Visiting Scientist at Dana-Farber/Harvard Medical School
Immunotherapy in Testicular Cancer: Were We Are and Perspectives
April, 4th, 2019
Introduction
• Testicular germ cell tumors are among the most chemo-sensitive solid
tumors
• A small proportion of patients fail to be cured with cisplatin-based
chemotherapy (3-4 cycles of BEP)
Indirect targeting of the tumor using the immune system
2013 2014
Cierna et al. Annals of Oncology 27: 300–305, 2016
Results
• PD-L1 expression:• 76% of seminomas
• 89% of non-seminomas
• The highest PD-L1 expression was found in choriocarcinomas, with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and the lowest expression in seminoma
• Dichotomized PD-L1 expression, only 20% of TGCTs had high PD-L1 expression (QS ≥ 10)
Cierna et al. Annals of Oncology 27: 300–305, 2016
PD-L1 expression is higher in patients with more advanced disease with poor prognostic features
Cierna et al. Annals of Oncology 27: 300–305, 2016
PFS according to PD-L1 expression
Cierna et al. Annals of Oncology 27: 300–305, 2016
Semaan, A et al. Immunotherapy: last bullet in platinum refractory germ cell testicular cancer. Future Oncology,2018
Semaan, A et al. Immunotherapy: last bullet in platinum refractory germ cell testicular cancer. Future Oncology,2018
Phase II trial of pembrolizumab in patients (pts) with incurable platinum refractory germ cell tumors (GCT)
Adra et al. J Clin Oncol 35, no. 15_suppl (May 20 2017) -NTC02499952
Results (N=12)
Adra et al. J Clin Oncol 35, no. 15_suppl (May 20 2017) -NTC02499952
Summary – Pembrolizumab in GCT
• Median # doses: 2 (1-8)• 6 grade 3 AEs• No partial or complete responses ORR=0%!• 2 patients had SD (radiologically) with rising AFP…
• (PD-L1 negative)
• 10 patients had PD• 2 patients with higher PD-L1 expression PD
Adra et al. J Clin Oncol 35, no. 15_suppl (May 20 2017) -NTC02499952
Cabozantinib + Nivolumab +Ipilimumab in GU Tumors
Nadal RM, et al. ASCO GU 2018: Abstr. 515.
Necchi et al. Eur Urol Focus (2018)
Seminoma Non-Seminoma
Necchi et al. Eur Urol Focus (2018)
Necchi et al. Eur Urol Focus (2018)
• Primary testicular lymphoma are rare extranodal large B-cell lymphomas. • Poor prognosis
• Frequent 9p24.1 copy number alterations associated increased expression of the programmed cell death protein 1 (PD-1) ligands PD-L1 and PD-L2.
• Activity of PD-1 blockade in other lymphomas with 9p24.1
1 complete response with Nivolumab
Ongoing Clinical Trials
Conclusion and Perspectives
• Germ cell tumors have excellent cure rates with standard treatment
• Small percentage of patients are refractory to several lines of chemotherapy
• Immunotherapy has not shown encouraging results so far, but may be a new hope
• Combinations with standard treatments?
• Biomarkers?
• TMB?
• MSI-High?
André P. Fay, MD, PhD
[email protected][email protected]
@DrAndreFay
Immunotherapy in Testicular Cancer: Were We Are and Perspectives