Clinical Trial Data With Perioperative Therapy in MIBC: HCRN GU 16-257

Transcript:

Shilpa Gupta, MD: The other study that was presented was by Matthew Galsky, MD, the HCRN GU 16-257. That was a similar approach, but it did not use biomarkers for selection. Could you walk us through the updates? Mamta and Andrea, feel free to pitch in if you would like to share your thoughts about that abstract that was presented at this ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium].

Petros Grivas, MD, PhD: I think overall it’s a great effort to try to make these trials a reality. The Hoosier Cancer Research Network [HCRN] trial, GU 16-257, is a phase 2 trial in the neoadjuvant setting using gemcitabine/cisplatin plus nivolumab and selective bladder sparing in patients with muscle-invasive bladder cancer, transurethral bladder tumor resection plus systemic therapy. We have been using this treatment for a long time. Some of those well-selected patients are able to maintain the bladder and have long-term disease-free survival. It’s interesting to see how we can better select those patients in the future by using this approach. Dr Galsky in this particular trial was trying to validate the surrogacy and how patients with clinical complete response do over time, with longer follow-up with bladder preservation, and I think that’s a big question. We need to validate our points over time, and I think the relevant point to make here is that if you think about pathological complete response in patients who get radical surgery, the question is how well that end point corresponds to overall survival.

Andrea has been leading many efforts with the NCCN [National Comprehensive Cancer Network] and the FDA trying to define this end point, the surrogacy value of those end points, pathologic complete response in those with radical surgery, and clinical complete response in those without surgery. Very briefly, in the GU 16-257 trial, patients got 4 cycles of gemcitabine/cisplatin plus nivolumab. They had muscle-invasive disease, T2, T3, and T4A, and after the 4 cycles they got clinical restaging with cystoscopy, biopsy, cytology, and imaging. Those with clinical complete response did not undergo cystectomy. They had nivolumab as a consolidation or maintenance therapy, and the others went to cystectomy. Those with no clinical complete response went on to cystectomy. I think the study was hypothesis generating so that the gemcitabine/cisplatin plus nivolumab combination after TVRBT [transurethral resection of bladder tumor] was associated with an interesting high clinical complete response rate. This was 43% in the initial report.

With longer follow-up, we see an interesting signal there, corroborating to a degree the results of the RETAIN study. In well-selected patients, some patients may do pretty well with clinical complete response rates. The challenge of course is how this translates to long-term survival. I think there is an interesting signal. The question is No. 1, can we validate that signal in bigger, larger studies and look more carefully at molecular biomarkers we can use to select our patients? That’s a challenging task. Maybe some composite approaches in the future using gene mutations, ctDNA [circulating tumor DNA], maybe some other imaging can help us select the right patients for active surveillance in the context of clinical complete response rate. The challenge, of course, is that many patients are understaged, and we don’t have accurate clinical staging. We need to improve upon that and standardize our definitions of how methodologically we assess clinical complete response.

Shilpa Gupta, MD: That is such a great point, Petros, and in this HCRN study, we saw that it was left up to patients to decide whether they wanted a cystectomy, and I think 30 out of 31 patients chose not to get a cystectomy. We all know patients don’t want a cystectomy, but as clinicians, we can’t say with 100% accuracy if that is the right approach or not. Using novel imaging and biomarkers is key to successfully determining that.

Transcript edited for clarity.