Efficacy of Adding Panitumumab to Dose-Dense MVAC Chemotherapy in Patients with Advanced Urothelial Cancer - Expert Commentary

Platinum-based chemotherapy is the cornerstone of initial treatment for most patients with advanced urothelial cancer (UC). EGFR is a promising target given its high expression levels in UC and the availability of anti-EGFRs inhibitors. However, it is unclear if adding an anti-EGFR inhibitor to platinum-based chemotherapy will lead to better clinical outcomes.

A recently published study by Culine et al. in Clinical Genitourinary Cancer investigated the efficacy and safety of adding the anti-EGFR monoclonal antibody panitumumab (Pmab) to dose-dense MVAC chemotherapy. The study included patients with pure UC or mixed histology except for the small cell variant. Eligible patients had HRAS or KRAS wild-type tumors. The investigators randomized 97 eligible patients to dd-MVAC (n=33) and dd-MVAC plus Pmab (n=63). All patients received a median of six cycles. No significant differences in serious adverse effects were observed between the two arms. No treatment-related deaths were reported.

The study did not meet its primary endpoint. The median progression-free survival was 5.7 months in the dd-MVAC plus Pmab arm compared to 6.8 months in the dd-MVAC arm (hazard ratio [HR], 1.6; 95% CI, 1.0-2.5). Similarly, the median overall survival was12.5 months in the dd-MVAC plus Pmab arm compared to 20.2 months in the dd-MVAC arm (HR, 1.81; 95% CI, 1.1-3.0). No significant difference in objective response rate was observed between the two arms. Overall, there was a trend toward worse clinical outcomes with the addition of Pmab.

The investigators used dual CK5/6–GATA3 immunostaining and RNA-based NanoString testing to identify the basal/squamous (BASQ) subtype in 73 and 50 patients, respectively. The rationale was that BASQ tumors harbor frequent EGFR gains and activation of an EGFR autocrine loop. No significant differences in the objective response rate and PFS were observed between BASQ and non-BASQ tumors.

The results of this trial add to previous studies of EGFR inhibitors in patients with UC and highlight the need for a deeper understanding of the role of EGFR in UC and analyses that identify biomarkers of oncogenic addiction to EGFR signaling UC tumors.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


Reference:

  1. Culine S, Fléchon A, Gravis G, Roubaud G, Loriot Y, Joly F, et al. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin With or Without Panitumumab in Patients With Advanced Urothelial Carcinoma: Multicenter, Randomized, French Unicancer GETUG/AFU 19 Study. Clin Genitourin Cancer. 2021;19(4):e216–22.


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