Episode 10: Enhancing neoadjuvant chemotherapy with immune checkpoint inhibition in MIBC: insights from the NEMIO Trial

Prof Emmanuel Seront from UCL Louvain discusses with Prof Christof Vulsteke from Maria Middelares Gent how the NEMIO trial improves neoadjuvant chemotherapy in the perioperative setting in MIBC patients.

In these cases, cisplatin-gemcitabine-based chemotherapy is SOC. However, given the correlation between higher pCR rates and improved outcomes, various approaches are being explored alongside ddMVAC. The NEMIO trial, a phase 1-2 study, investigates adding the immune checkpoint inhibitors durvalumab (D) with or without tremelimumab (T) to ddMVAC in MIBC patients. Around 120 cT2-4N0-1 patients were randomized into two arms, receiving 4 cycles of ddMVAC every 2 weeks with D +/- T every 4 weeks.

The primary endpoint, pCR, was approximately 49% in the doublet therapy and 47% in the triplet therapy, indicating no additional benefit from adding T to ddMVAC and D. Impressively, DFS reached 80% in the doublet and 90% in the triplet therapy after 1 year of follow-up.

Ensuring safety was a significant co-primary endpoint, with the majority of patients (>75%) completing treatment cycles and undergoing radical cystectomy. Only 6 patients did not receive cystectomy, with 4 refusing and 2 experiencing disease progression. This marked improvement compared to earlier trials, where only 60% of patients completed all treatment cycles, underscores the promise of these results, despite the absence of a control arm such as ddMVAC alone. The safety profile warrants further investigation in phase 3 studies.

Experts note the challenge of achieving over 50% pCR in all trials in this patient cohort, despite the NEMIO trial achieving one of the highest rates among clinical trials conducted. Increased pCR was associated with pathological downstaging, as only one-third of patients had residual tumours in the blood.

To surpass the 50% pCR threshold, trials combining checkpoint inhibition with EV may be promising, as pathological downstaging is anticipated. In the first-line metastatic setting, EV-pembrolizumab offers hope for cisplatin-ineligible patients. In the context of the NEMIO trial, patients need to be fit enough for chemotherapy and have good renal function. To conclude, exciting results are anticipated in the perioperative setting.