ASCO 2017: Phase II trial of pembrolizumab in patients (pts) with incurable platinum refractory germ cell tumors (GCT)

Chicago, IL (UroToday.com) While patients with testicular cancer often have very high cure rates in the cisplatin era, even in the setting of relapsed disease, many can often be salvaged with standard-dose (SDCT) or high-dose chemotherapy (HDCT). However, up to 15% of patients with relapsed GCT are not curable, and it is in these patients that novel HDC regimens or alternative regimens are needed.

Immune checkpoint blockage using novel immune checkpoint inhibitors effectively counteracts a tumor’s immune evasion tactics and re-sensitizes a patient’s immune system against the tumor. With promising results in many solid organ malignancies, such as breast, melanoma and bladder cancer, there has been interest in assessing its utilities in other advanced malignancies. Pembrolizumab, one of the primary agents approved for other malignancies, specifically targets PD-1, the receptor in the most commonly targeted immune checkpoint pathway.

In this phase II multi-institutional trial, twelve men with no salvage therapy options were treated with intravenous pembrolizumab 200mg IV Q3weeks until disease progression. All these patients had failed / progressed after first line cisplatin-based chemotherapy and at least 1 salvage regimen (HDCT or SDCT). Simon’s 2-stage design required response in ≥ 1/12 pts to proceed – in the second stage, an additional 8 patients were enrolled. The total cohort was finally 20. The primary endpoint was overall response rate using immune-related response criteria.

As with many other immune checkpoint studies, this study included an assessment of PD-1 status. Specifically, PD-1 status on tumor infiltrating immune cells was centrally assessed using a PD-L1 (22C3) assay, and was then scored as 0, 1, 2, 3 along with PD-L1 expression score (H-score) incorporating intensity of staining. Patients were eligible irrespective of PD-L1 expression status. Of the patients included, only 2 pts had positive PD-L1 staining (H-score 90 and 170).
The twelve initial patients were aged 27-55, all the patients had non-seminoma GCT, the primary tumor site was testis in 11 pts and mediastinum in 1, median AFP 615 (range, 1-32,760) and hCG 4 (range, 0.6-37,096), median number of prior chemotherapy regimens was 3, and 6 had received prior HDCT. Six of the patients had had a late relapse (>2 years). Ultimately, this was a high-risk group with poor prognosis.

In terms of tolerability, median number of deliverable pembrolizumab doses was 2 (range, 1-8). There were 6 grade 3 adverse events, with 4 events possibly related to study treatment (chest pain, hyperglycemia, abdominal pain). However, there were no immune related adverse events.

Unfortunately, no partial or complete responses were observed. Two patients achieved stable disease for 12 and 9 weeks respectively; 10 pts had progression of disease as their best response. The two patients with stable disease had continued rising AFP level despite radiographic stability; both had negative PD-L1 staining.

Based on these results, in this first study to assess the role of immune checkpoint blockade in GCT, pembrolizumab did not appear to have any clinical benefit despite being well tolerated. The only two patients with stabilized radiographic disease continued to have rising tumor markers.

As previous studies in GU malignancies have demonstrated, PD-1 status is not an ideal predictor of response.

Presented By: Nabil Adra

Co-Authors: Sandra K. Althouse, Natraj Reddy Ammakkanavar, Milan Radovich, Costantine Albany, David J. Vaughn, Lawrence H. Einhorn, Nasser H. Hanna

Institution(s): Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Indiana University School of Medicine, Indianapolis, IN; Community Cancer Center, Indianapolis, IN; Abramson Cancer Center, Philadelphia, PA

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @tchandra_uromd

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA
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