ASCO 2017: Infusional gemcitabine + docetaxel/melphalan/carboplatin (GemDMC) ± bevacizumab (BEV) as an effective high-dose chemotherapy (HDC) regimen for refractory of poor-risk relapsed germ-cell tumors (GCT)

Chicago, IL (UroToday.com) While patients with testicular cancer often have very high cure rates in the cisplatin era, a small population of patients who have poor-risk germ cell tumors (GCT) and relapse despite initial chemotherapy or are refractory to initial treatment regimens have poor prognosis. While high-dose chemotherapy (HDC) with carboplatin and etoposide has been effective in some patients, it is not effective in all patients.

Based on the premise that DNA damage repair inhibition may help salvage some of these high-risk GCT patients with relapsed or refractory disease, the authors of this study initiated a trial of a novel HDC regimen: Infusional gemcitabine + docetaxel/melphalan/carboplatin (GemDMC) ± bevacizumab (BEV). They included BEV due to potential synergy with the other chemotherapy agents, and due to the high vascularity of GCT metastases. HDC included BEV (5 mg/kg) preceding GemDMC (HDC #1) and ifosfamide/CE (ICE) (HDC #2).

Inclusion criteria: Intermediate (int)/high-risk patients (based on Beyer Model1), creatinine ≤1.8 mg/dL and adequate organ function.

Following treatment of 42 patients with BEV, the remaining 27 patients were treated without BEV. The total number of patients treated were 69. There were no significant differences between the two groups, and in general, patients were 28-30 years old, 76-85% had testis primary tumors (11-15% mediastinal, 4-10% retroperitoneal), 90% had a < 3 month progression-free survival prior to treatment, 2+ relapses, and were cisplatin refractory.

The key outcomes from the entire cohort were as follows. Tumor markers normalized in 90% of patients with active tumors at the time of HDC. After HDC, 19 pts achieved complete response (CR) and 28 had partial response without metastases (PRm-). Of these 28, 22 had residual lesions resected with no viable tumor found in 20/22, 2 had xRT, and 4 were monitored. Median follow-up was 39 months (range 2-105). The 2-year recurrence free survival (RFS) rates in cohorts 1 and 2 = 52% and 78%, respectively. Their respective 2-year OS rates were 55% and 81%.

From a tolerability standpoint, the main AE’s were mucositis and renal (4 HDC-related deaths in cohort 1, 1 in cohort 2).

Looking at cohort 1 vs. cohort 2, cohort 1 did not achieve any improvement in oncologic outcomes, but added toxicity. Based on this, the addition of BEV did not seem to be warranted.

However, as an alternative to carbo/etoposide, this new HDC regimen appears to be promising. Unfortunately, it does not provide a direct comparison to the current standard.

Limitations / Discussion Points:
1. No comparison to current standard therapy. Uncertain if there is any oncologic benefit compared to the standard.

While further studies are required, this preliminary assessment in a heavily pretreated highly refractory group of patients with active GCT generated promising results.

Presented By: Yago Nieto

Co-Authors: Shi-Ming Tu, Matthew T. Campbell, Roland Bassett, Nizar M. Tannir, John Francis Ward, Wayne Lewis Hofstetter, Roy B. Jones, Borje Andersson, Alison M Gulbis, Celina Ledesma, Melissa Timmons, Michelle Trapp, Richard E. Champlin, Lance C. Pagliaro

Institution(s): The University of Texas MD Anderson Cancer Center, Houston, TX;
Mayo Clinic, Rochester, MN

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

REFERENCES:
1. Beyer J, Kramar A, Mandanas R, et al. High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables. J Clin Oncol. 1996;14(10):2638–2645.
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