Neoadjuvant avelumab plus cisplatin-based chemo confers high OS, EFS rates in MIUC

The combination of avelumab and cisplatin-based chemotherapy as neoadjuvant therapy for muscle-invasive urothelial carcinoma (MIUC) yields high overall survival (OS) and event-free survival (EFS) rates at both 1 and 3 years, according to the survival data from the dual-cohort, phase II AURA trial presented at ASCO 2024.

The 12-month OS rates with the two avelumab-incorporating cisplatin-based regimens before radical cystectomy were >90 percent. The preliminary 36-month OS rate was as high as 64 percent with avelumab plus gemcitabine-cisplatin (GC) and 85 percent with avelumab plus dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC). [ASCO 2024, abstract 4516]

The EFS rate at 12 months was 84 percent with avelumab plus GC and 92 percent when avelumab was added to dd-MVAC. At the preliminary 36-month mark, the EFS rates were 62 and 79 percent with the two regimens, respectively.

While the OS and EFS rates appeared to be higher with the avelumab plus dd-MVAC regimen, formal statistical testing was not conducted as the trial was not designed to compare outcomes between regimens.

AURA was a non-comparative, randomized study conducted at 10 centres in Belgium and France. Patients with MIUC were stratified into two cohorts based on their eligibility for cisplatin. [BMC Cancer 2021;21:1292]

In the cisplatin-eligible cohort, 79 patients were randomized to receive either neoadjuvant avelumab plus GC or avelumab plus dd-MVAC.

The primary endpoint of pathologic complete response (pCR) rate had been previously presented. [ESMO 2021, abstract 659MO; ASCO 2022, poster 4517] The current analysis focused on the secondary endpoints of OS and EFS at 12 and 36 months. The association between achieving a pCR and OS was also explored.

Avelumab-incorporating non–cisplatin-based regimens

AURA also addresses an unmet need with its other cohort that employs avelumab in a cisplatin-ineligible population. "Until now, there have been no alternative systemic therapies available for these patients," said Dr Jeremy Blanc from the Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium.

In this cohort, 56 patients were randomized to receive either preoperative single-agent avelumab or avelumab plus paclitaxel-gemcitabine.

The 12-month OS rates were 79 percent with single-agent avelumab and 82 percent with avelumab plus paclitaxel-gemcitabine. For EFS at 12 months, the corresponding rates were 64 and 60 percent, respectively.

These results generally suggest a lack of additional benefit from incorporating paclitaxel-gemcitabine with avelumab. Longer follow-up is required for a 36-month survival analysis.

pCR tied to improved OS

Achieving a pCR was associated with longer OS, particularly with the avelumab plus dd-MVAC regimen in the cisplatin-eligible cohort (p=0.0085) and with single-agent avelumab in the cisplatin-ineligible cohort (p=0.0023). Of note, no patients randomized to avelumab plus dd-MVAC who achieved pCR died within 36 months.

“Further investigation through phase III trials is very important to validate our findings,” concluded Blanc.