Phase II clinical trial for GEM+CIS+Immunotherapy for MIBC

4 months 2 days ago - 4 months 2 days ago #62019 by sara.anne
Joe, once again, you have shared a very important article with us. Thank you! This clinical trial could be critical as long as they are very careful in selecting patients.

Sara Anne

Diagnosis 2-08 Small papillary TCC; CIS
BCG; BCG maintenance
Vice-President, American Bladder Cancer Society
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4 months 2 days ago #62018 by joea73
Phase II clinical trial of  Gemcitabine, Cisplatin chemotherapy plus Nivolumab PD-1 checkpoint inhibitor immunotherapy to treat  muscle invasive bladder cancers (MIBC) as another bladder preservation treatment instead of radical cystectomy was published in Nature communication.

www.nature.com/articles/s41591-023-02568-1

Today, the standard treatment protocol for MIBC is radical cystectomy and for some patients meeting specific conditions, e.g.. a sole and small T2 tumor and no CIS, the trimodal treatment (TMT)  which consist of another TURBT, chemotherapy and radiation is being offered.  Massachusetts General Hospital in the US and University of Toronto in Canada are well know for TMT in each country,   The data has shown that if patients are carefully chosen, TMT should give equivalent efficacy to RC.  

The Phase II clinical trail of GEM+CIS+Nivolumab enrolled wider range of patients compared to more restricted patients selection for TMT.   

 Neoadjuvant chemotherapy (GEM+CIS) for RC has shown complete response to 30% of patients.    Often the pathological complete response is  discovered after RC by examining organs and tissues obtained from the surgery.    The  Phase II trial is to compare the effectiveness of administering immunotherapy Nivolumab to those patients considered to have experienced complete response by using various diagnostics such as imaging vs going ahead with RC.

Selected patients :   

Cisplatin-eligible patients with cT2–T4aN0M0 MIBC received treatment with four cycles of gemcitabine and cisplatin plus nivolumab  followed by clinical restaging. 

Clinical restaging comprised magnetic resonance imaging (MRI) of the abdomen and pelvis (unless contraindicated, in which case computed tomography (CT) scans were substituted), CT of the chest, cystoscopy with biopsies according to a recommended template and urine cytology.  

A clinical complete response (cCR )was defined as (1) no evidence of high-grade malignancy on biopsy; (2) no malignant cells on urine cytology; and (3) no definitive evidence of local or metastatic disease on cross-sectional imaging.

Participants with clinical complete response (cCR) was given a choice for RC or Nivoumab.    

33 patients had cCR, and 32 chose Nivolumab and 1 chose RC
39 patients  did not have cCR, and 34 chose RC and 4 chose radiation.

Patients with cCR showed about 95% survival at 40 months and 90% without metastasis at 40 months.
Patients without cCR showed about 60% survival and  65% without metastasis at 40months.

The clinical trial also studied genomic profile of those had cCR, which I have not understood fully at this time. 

The report concluded in saying that In our study, neoadjuvant gemcitabine, cisplatin, plus nivolumab after TURBT was associated with a cCR rate of 43%, and clinical response assessment identified patients with particularly favorable outcomes and facilitated bladder sparing. Genomic, imaging and immunological biomarkers have the potential to refine this treatment paradigm, but they require further investigation. These findings may help advance a more personalized approach to the management of MIBC.


Currently, the most recent adopted and FDA approved  protocol for MIBC is to have GEN/CIS neoadjuvant chemotherapy, followed by RC, followed by Nivolumab immunotherapy.  This phase II clinical trial is the same except RC is not done for those who had cCR after neoadjuvant chemotherapy.    Hope  the Phase II results indicate more bladder preservation opportunities for MIBC patients.

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