Safety and Efficacy of OncoTherad Nano-immunotherapy in Patients with Non-Muscle Invasive Bladder Cancer

Abstract

Abstract The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom Bacillus Calmette-Guerin (BCG) has failed or is contraindicated are recently increasing due to the development of new drugs. In this scenario, a new perspective is represented by OncoTherad nano-immunotherapy. We carried out a prospective, single-center (Municipal Hospital of Paulínia, São Paulo, Brazil), single-arm phase I/II study (Clinical Trial: RBR-6swqd2) in 29 (18 male, 11 female) patients with BCG-refractory, relapsed or intolerant NMIBC (≥ 1 previous course of BCG therapy). The median age of the 29 patients and follow-up were 65 years (range 34-96) and 24 months, respectively. OncoTherad treatment showed complete response of 79.3% and recurrence-free survival of 22.2 months at 24-month follow-up. Regarding toxicity, 62.1% of adverse events were Grade 1 or 2. The most commonly reported treatment-related adverse events were dysuria, cystitis, pruritus, rash, arthralgia and fatigue. Also, this study demonstrated an important effect of activation of the Toll-like Receptor 4 (TLR4) signaling pathway triggered by OncoTherad in the formation and organization of primary lymphoid follicles in most patients at 24-months follow-up, which may be related to antitumor and immunoprotective effects from this immunotherapy in bladder tissue. In conclusion, OncoTherad nano-immunotherapy seems a safe and effective treatment option for BCG-relapsed and/or intravesical chemotherapy-relapsed NMIBC patients and may provide benefit for preventing tumor recurrence.