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Título

BIOLOGICAL RESPONSE MODIFIER - INORGANIC PHOSPHATE COMPLEX 1 (ONCOTHERAD) FOR THE TREATMENT OF PATIENTS WITH BACILLUS CALMETTE-GUERIN-UNRESPONSIVE, HIGH-RISK NON–MUSCLE INVASIVE BLADDER CANCER: A NEW GOLD STANDARD TREATMENT?

Resumo

The standard of care for high-risk non-muscle-invasive bladder cancer (HRNMIBC) after transurethral resection of the bladder tumour is intravesical Bacillus Calmette-Guérin (BCG). However, despite high initial responses rates, up to 40% of patients have recurrence or become BCG-unresponsive. Biological Response Modifier - Inorganic Phosphate Complex 1 (OncoTherad) is a nanostructured inorganic phosphate complex associated with glycosidic protein, which leads to stimulation of the immune system mediated by Toll-like Receptors 2 and 4, resulting in an increased activation of the interferon signaling pathway, and represents a promising therapeutic perspective for BCG-unresponsive NMIBC. Thus, the aims of this study were to evaluate the safety and efficacy of OncoTherad immunotherapy for BCG-unresponsive NMIBC. We carried out an open-label, single-center (Municipal Hospital of Paulinia, SP, Brazil) and single-arm phase 1/2 study (Clinical Trial: RBR-6swqd2) in 44 (30 male, 14 female) patients with BCG-unresponsive NMIBC. OncoTherad schedule was initiated with weekly intravesical (120 mg/mL) and intramuscular (25 mg/mL) treatment for 6 consecutive weeks, followed by one every other week application for 3 months and, one monthly application until the end of the treatment (24 months). The primary endpoints were pathological complete response (pCR) rate (absence of HRNMIBC or progressive disease) and recurrence-free survival (RFS). Secondary endpoints were duration of response (DOR) and safety. Patient follow-ups were performed with systematic mapping biopsies of the bladder, cystoscopy and ultrasound every 3 months for the first year and every 6 months thereafter for up to 2 years. The median age of the 44 patients and follow-up were 65 years (range 34-96) and 24 months, respectively. At 24-months follow-up, pCR rate was 72.7% (95% CI) and RFS of 21.4 months. Among 32 patients with CR, the median DOR was 13.5 months. No patient’s disease progressed to muscle-invasive or metastatic bladder cancer while on study treatment. Grade 1/2 treatment-related adverse events (TRAEs) occurred in 63.7% of patients; most frequently reported TRAEs were dysuria (52.3%), pruritus (50.0%), cystitis (43.2%), arthralgia (34.1%), fatigue (31.8%) and rash (27.6%). Grade 3/4 TRAEs occurred in 6 patients (13.6%). In conclusion, OncoTherad immunotherapy seems a safe and effective treatment option for BCG-unresponsive NMIBC patients and may provide benefit for preventing tumor recurrence.

Palavras Chave ( separado por ; )

Bladder cancer; Immunotherapy; OncoTherad; Nanotechnology

Área

Uro-oncologia