A phase I study of chemoradiation with weekly panitumumab following neoadjuvant chemotherapy and pelvic lymph node dissection as an organ preserving treatment of invasive bladder cancer.

Abstract

392 Background: Radical Cystectomy (RC) is the standard treatment of Invasive Bladder Cancer (IBC). Although organ sparing, external beam Radiation Treatment (RT) alone is considered inferior to RC. Since the Epidermal Growth Factor receptor (EGFr) is frequently overexpressed in IBC, combined EGFr inhibition by Panitumumab (P) and RT might improve treatment outcome. In this study, the safety and efficacy of concurrent RT and P (RT/P) following Neoadjuvant Chemotherapy (NAC) and Pelvic Lymph Node Dissection (PLND) was evaluated. Methods: cT2-4N0-2M0 or cT1N1-2M0 bladder cancer patients were enrolled in the study. NAC consisted of a maximum of 4 cycles platinum-based chemotherapy. cN0 patients received NAC after PLND, while cN+ patients (confirmed by fine needle aspiration) received NAC prior to PLND. RT/P consisted of concurrent P (7 weekly doses of 2.5 mg/kg) and bladder RT (66Gy in 33 fractions). Primary end-points were treatment-related toxicity and complete clinical response (CR) assessed by Computed Tomography and cystoscopy 3 months after therapy completion. Partial response (PR) was defined as cT < 2N0. Results: A total of 31 patients were included (mean age: 60±10 years), 3/31 patients were cN1-2. Three patients discontinued NAC after 3 cycles due to toxicity. After NAC (24 cisplatin-based and 7 gemcitabine/carboplatin) 13 (41.9%) patients had remaining visible disease. All patients completed RT, while 4/31 patients terminated P prematurely (2-6 doses) due to toxicity. Preliminary response results after RT/P were available for 29/31 patients. Twenty-six/29 (89.7%) patients had a CR, 3 patients PR (10.3%) of which 2 were treated with transurethral resection and intravesical treatment (TaG1-2) and 1 patient underwent immediate cystectomy after histologic confirmation of T1G3. Conclusions: These preliminary results suggest that concurrent P and RT following NAC and PLND is an organ-preserving option for IBC. Toxicity, EGFr expression, mutational status and long-term oncologic outcomes have to be awaited. Clinical trial information: NL31148.031.10.