Differing Trial Designs for Immunotherapy in MIBC Yield Favorable Outcomes

EP: 1.Nivolumab Shows Improved DFS in ITT and PD-L1–High Bladder Cancer

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EP: 4.Differing Trial Designs for Immunotherapy in MIBC Yield Favorable Outcomes

Rana R. McKay, MD, professor of medicine and urology at UC San Diego School of Medicine, discusses the significance of clinical trial data for immunotherapy in muscle-invasive bladder cancer (MIBC) treatment she presented at a Case-Based Roundtable event.

At the event, she discussed data such as an update from the CheckMate 274 trial (NCT02632409) of nivolumab (Opdivo) vs placebo as adjuvant therapy for MIBC. The overall survival (OS) data favored nivolumab in the intent-to-treat population and even more strongly in the population of PD-L1 expression 1% or higher. Investigators in the AMBASSADOR/A031501trial (NCT03244384) reported disease-free survival (DFS) benefit with pembrolizumab (Keytruda) vs observation in the neoadjuvant setting but OS data were immature. This trial was notable for allowing patients with positive margins after resection to enroll.

McKay also brought up the NIAGARA trial (NCT03732677) of durvalumab (Imfinzi) plus neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone. She said this study allowed patients with a creatinine clearance of greater than 40 mL/min per 1.73 m², a lower threshold than some other studies. The durvalumab arm had superior event-free survival, but she said questions remained since these patients received durvalumab before and after resection. It did not investigate whether patients could avoid adjuvant immunotherapy following a pathologic complete response (pCR). Additionally, the comparator arm did not receive any adjuvant immunotherapy although other studies have now shown this to be beneficial.

TRANSCRIPTION:

0:10 | There was a lot of discussion around the role of adjuvant immunotherapy for people with high-risk localized MIBC at the time of cystectomy, evolving data from CheckMate 274, now we see longer-term follow-up data. We've seen OS data that certainly appear to be suggesting that patients may derive an OS benefit with this regimen, particularly those individuals [who] are PD-L1 positive. With the AMBASSADOR study, definitely positive trial with regards to DFS. This was a study that looked at adjuvant pembrolizumab—some slight differences with the enrollment criteria in that this trial did allow patients with positive surgical margins to enroll. The DFS was positive for pembrolizumab. The OS data are still immature.

1:00 | We also chatted about the NIAGARA data of perioperative durvalumab/cisplatin-based chemotherapy in the perioperative setting. The uniqueness of this study was it actually allowed enrollment of patients with a GFR [glomerular filtration rate] of greater than 40 [mL/min per 1.73 m2] so it had a slightly lower GFR threshold than historically utilized, and patients received cisplatin, gemcitabine, durvalumab, pre- and post- surgery and the post-surgery treatment was not dependent on pathologic responses at the time of surgery, and the control arm patients did not receive adjuvant immunotherapy. So there are some questions that are left unanswered with the NIAGARA study, particularly around [whether] patients with a pCR need outback treatment, and then what's the performance of the control arm in the context of adjuvant immunotherapies now demonstrating improvements in outcomes?