Phase 2 open label study of durvalumab with neoadjuvant chemotherapy in variant histology bladder cancer

• Published in: Journal of clinical oncology Vol. 41; no. 6_suppl; p. 524
• Main Authors: Khaki, Ali Raza, Fan, Alice C., Shah, Sumit, Parikh, Divya Ahuja, Chien, Joanne, Moore, Kaidi, Ruiz, Shann Mika, Haas, Denise, Fakhoury, Laith, Del Toro, Noël, Baker, Paige, O'Brien, Aidan, Srinivas, Sandy
• Format: Journal Article
• Language: English
• Published: American Society of Clinical Oncology 20.02.2023
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2023.41.6_suppl.524

524Background: The immune-responsive nature of bladder cancer has made it an active area of interest for novel applications of immune checkpoint inhibitors (ICIs), with multiple ICI agents approved in the metastatic setting and ongoing perioperative trials. Variant histology urothelial carcinoma is a rare, heterogenous, and aggressive disease category associated with poor prognosis and response to standard therapies. This investigator-initiated phase 2 trial explored the addition of durvalumab to neoadjuvant chemotherapy (NAC) in the setting of variant histology MIBC. Methods: Patients with cT2-T4a, N0-N1, M0 histologically-confirmed bladder cancer of variant histology who were candidates for platinum-based NAC and radical cystectomy were eligible for the study. Enrolled patients received durvalumab with each cycle of investigator's choice of platinum NAC (ddMVAC, cisplatin/gemcitabine, or carboplatin/gemcitabine). The primary objective was to determine the safety and tolerability of each study treatment as assessed by the total number of adverse events of grade 3 or higher, judged by the investigator as probably or definitely related to durvalumab. Secondary objective was to determine the percent of subjects post neoadjuvant chemo immunotherapy who achieve tumor stage of pT2N0M0 or better at cystectomy. Target accrual was 24 patients. Results: Six patients were enrolled (the study closed early due to low accrual). Median age was 72 years, 17% were women, 67% were white, 33% were Asian. 50% received ddMVAC and 50% received carboplatin/gemcitabine. All patients completed the planned cycles of NAC and durvalumab (4 cycles) and 5/6 proceeded to radical cystectomy (one patient declined cystectomy). Three patients experienced a Grade 3 AE that was assessed by the investigator to be related to treatment (table). One patient with sarcomatoid and glandular histology had pathological complete response and one patient with papillary and 10% squamous had pT2N0 at cystectomy. Conclusions: The addition of durvalumab to platinum NAC for patients with variant-histology muscle invasive bladder cancer demonstrates a reasonable safety and tolerability profile. Further investigation into this combination is warranted in larger scale trials. Clinical trial information: NCT03912818. PatientHistologyArm Initial tumor grade≥ Grade 3 CTCAEv5 probably or definitely related to treatmentFinal tumor gradeSCI-001Predominant sarcomatoidCarboplatin/gemcitabine + durvalumabcT2pT3N0SCI-002Predominant squamousCarboplatin/gemcitabine + durvalumabcT2G3 anemiaN/A (no RC)SCI-003Predominant plasmacytoidddMVAC + durvalumabcT2pT3N0SCI-005Minority squamousCarboplatin/gemcitabine + durvalumabcT2G3 neutrophil count decreasedpT2N0SCI-006Minority squamousddMVAC + durvalumabcT2G3 hypomagnesemiapT3bN1SCI-007Glandular and sarcomatoidddMVAC + durvalumabcT2N0M0ypT0N0 Note: Subject SCI-004 was a screen fail.