ASCO GU 2019: Gemcitabine-Carboplatin versus Gemcitabine-Oxaliplatin In Cisplatin Un-Fit Advanced Urothelial Carcinoma: Randomized Phase II Study-COACH Study

San Francisco, CA (UroToday.com) The first line chemotherapy in advanced metastatic urothelial carcinoma is cisplatin-based. The two most accepted options are gemcitabine + cisplatin (GC) or Methotrexate, Vinblastine, Doxorubicin, Cisplatin (MVAC). In patients who are unfit to receive cisplatin-based chemotherapy (approximately 30-50% of patients), the available options include gemcitabine and carboplatin, or immune checkpoint inhibitors such as pembrolizumab or atezolizumab for patients with high PD-L1 expression. Gemcitabine and carboplatin have been shown to harbor significant adverse events such as neutropenia (52.5%), thrombocytopenia (48.3%), febrile neutropenia (4.2%), grade 3 or 4 infections (11.8%), and severe acute toxicity (9.3%).^{^1,2}

There have been several trials assessing the efficacy of gemcitabine and oxaliplatin in advanced urothelial cell carcinoma as a better alternative. These have shown an objective response rate for this combination to range between 47-60%, and a median overall survival rate ranging between 6.5-15 months, as shown in table 1.

Table 1- Efficacy of gemcitabine + oxaliplatin in advanced urothelial carcinoma patients
UroToday ASCOGU2019 COACH study 1

In this rapid abstract presentation, Dr. Lee presented the COACH trial, which randomizing advanced urothelial carcinoma patients unfit for cisplatin-based chemotherapy to either Gemcitabine + carboplatin, or gemcitabine + oxaliplatin, Clinical trial information: NCT01487915 (Figure 1).

Figure 1 -Trial design:
UroToday ASCOGU2019 COACH study 2

This study took place in eight tertiary academic centers between 2013 and 2017. The primary endpoint was response rate, and the secondary endpoints included progression-free survival, overall survival, and toxicity. The demographic and clinical data are shown in table 2. The overall response rate was shown to be 49% in the gemcitabine + carboplatin arm vs. 55% in the gemcitabine + oxaliplatin arm. The carboplatin arm seemed to be less active in patients with creatinine clearance of less than 30 ml/min while the oxaliplatin arm had preserved activity in these patients (figure 2).

Table 2 – Demographic and clinical data:
UroToday ASCOGU2019 COACH study 3

Figure 2 -Efficacy endpoints:

The toxicity data demonstrated that while almost all toxicities were lower in the oxaliplatin arm, the oxaliplatin patients did have a considerably higher percentage of peripheral neuropathy (52.5% vs. 7.7%), with only 7.5% being defined as grade 3, and none had grade 4.

In conclusion, the gemcitabine + oxaliplatin regimen demonstrated comparable efficacy with the gemcitabine + carboplatin regimen, and favorable hematologic toxicity profile, at the expense of an increased rate of peripheral neuropathy. Dr. Lee concluded that Oxaliplatin may be used as a new option for patients who are not suitable for platinum-based chemotherapy.

Presented by: Jae-Lyun Lee, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan, at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

References:

De Santis et al.Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986.J Clin Oncol.2012 Jan 10;30(2):191-9. doi: 10.1200/JCO.2011.37.3571. Epub 2011 Dec 12.
Poplin et al.Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group.J Clin Oncol. 2009 Aug 10;27(23):3778-85. doi: 10.1200/JCO.2008.20.9007. Epub 2009 Jul 6.

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