MP61-08 A PHASE I/II TRIAL OF TRANSURETHRAL SURGERY FOLLOWED BY A COMBINATION OF ATEZOLIZUMAB AN ANTI-PDL-1 (MPDL3280A) WITH TRIMODAL THERAPY IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER

Abstract

INTRODUCTION AND OBJECTIVE: Bladder preserving strategies such as trimodality therapy (TMT) remain associated with suboptimal local control of muscle invasive bladder cancer (MIBC). Recently, immune checkpoint programmed death-ligand 1 therapy (PD-L1) has shown rapid and lasting responses in metastatic MIBC. Our aim was to evaluate safety and toxicity profile of concurrent Atezolizumab (anti-PDL-1) in combination with TMT in patients with MIBC. METHODS: Phase I/II non-randomized safety/efficacy study including T2-T4a N0M0 MIBC patients electing for bladder preservation therapy (NCT03620435). Patients were treated with a trans-urethral resection of bladder tumor (TURBT) followed by intensity modulated radiation therapy (IMRT) (50 Gy/20 fractions. 2.5 Gy per fraction – 5 times per week for 4 weeks), Gemcitabine (for 4 weeks at 100 mg/m2, IV once weekly) and Atezolizumab (1200 mg IV on day 1 of 3 week cycle). This trial recruited patients par block of 3 to assess dose related toxicity (DLT) in case of severe side effects the atezolizumab dose was reduced to 840mg. The primary endpoint was safety assessed using the national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 4.03. RESULTS: Between December 2017 and January 2019, our study included 8 patients (6 males); median age was 68 (IQR 60; 70). Six patients were cT2 and 2 patients cT3. The first five patients received atezolizumab at 1200 mg and 3 of them developed grade 3 side effects (table 1). The atezolizumab dose was reduced to 840 mg for the 3 last. Study was terminated due to the presence of grade 3 side effects even with the reduced atezolizumab dose. No grade 4 side effects were observed. No deaths occurred. CONCLUSIONS: Concurrent administration of immune checkpoint inhibition with chemoradiation for MIBC was associated with unacceptable toxicity. These results do not support their concurrent use with trimodality therapySource of Funding: Sponsored by F. Hoffmann-La Roche Ltd