A phase II trial of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy: clinical and pathological results

OBJECTIVE To evaluate the clinicopathological efficacy of neoadjuvant erlotinib (an epidermal growth factor receptor, EGFR, inhibitor) for invasive bladder cancer in patients undergoing radical cystectomy (RC) as despite definitive surgical therapy, only half of patients undergoing RC will have long-term disease-free survival, and effective adjunctive therapies, especially using agents with lower toxicity, would be a significant advance in the treatment of invasive bladder cancer. PATIENTS AND METHODS The primary endpoint of this phase II trial is to determine the effect of neoadjuvant erlotinib (150 mg once daily for 4 weeks) before RC on the pathological complete response rate (pT0 rate) in RC specimens. In addition, the safety of therapy with erlotinib was also evaluated. Patients selected for study included those with histologically confirmed muscle-invasive bladder cancer who had undergone initial transurethral resection. RESULTS In all, 20 patients with clinical stage T2 disease had neoadjuvant erlotinib therapy followed by RC. On surgical pathology, five patients (25%) were pT0; in addition, seven (35%) were clinically down-staged (< pT1) and 15 (75%) had organ-confined disease at surgical pathology. At a mean follow-up of 24.8 months, 10 patients remain alive and with no evidence of disease, four with organ-confined disease had progression and nine died, including six from disease and three from other causes. Erlotinib was tolerated in all patients, with drug rash being the most common side-effect, in 15 patients (75%). Interestingly, all pT0 and pTis/T1 patients had a rash. CONCLUSIONS The EGFR inhibitor erlotinib, when administered in the neoadjuvant setting, can have beneficial effects in terms of surgical pathology and short-term clinical outcomes in patients undergoing RC for invasive bladder cancer. Analyses are underway to examine the molecular correlates of the apparent clinical effect of neoadjuvant therapy in these patients.