Combining the immunotherapy avelumab (Bavencio) with standard neoadjuvant chemotherapy induced pathological complete responses (pCRs) in over half of patients with nonmetastatic muscle-invasive bladder cancer (MIBC), according to findings from the phase 2 AURA trial presented during the 2021 ESMO Congress.1
Patients were randomized to avelumab (A) plus cisplatin-gemcitabine (CG + A) or dose-dense MVAC (DD-MVAC) plus A. The MVAC regimen comprises methotrexate (M), vinblastine (V), Adriamycin (A), and cisplatin (C). Across all patients in the study, 57% achieved a pCR and 61% of patients were downstaged to <ypT2N0.
The pCR rate was 54% in the CG + A arm, with 57% of patients downstaged to <ypT2N0. Among patients receiving DD-MVAC + A, the pCR rate was 61%, with 64% of patients downstaged to <ypT2N0.
“This phase 2 trial is the first evidence of avelumab in the neoadjuvant bladder cancer setting showing high pCRs when used in combination with standard chemotherapy. These combinations were safe and did not compromise surgical resection,” said lead study author Nieves Martinez Chanza, MD, PhD, a medical oncologist in the Oncology Medicine Department at Jules Bordet Cancer Institute, Brussels, Belgium.
The prospective, multicenter, noncomparative randomized phase 2 AURA trial enrolled patients with cT2-4aN0-2M0 MIBC who were scheduled to receive radical cystectomy and lymphadenectomy. The data shared during ESMO were for 56 patients, 28 of whom were randomized to CG + A and 28 of whom were randomized to DD-MVAC + A.
In the CG + A arm, the median age was 69 years (range, 41-81) and 64% were male. Twenty-five patients had pure urothelial carcinoma and 3 patients had mixed histology, defined as squamous differentiation with a predominant urothelial component (>50%). Regarding clinical stage at baseline, 18 patients were T2N0, 5 were TxN+ (evidence of lymph-node involvement), 3 were T3N0, and 2 were T4N0.
Among patients receiving DD-MVAC + A, the median age was 62 years (range, 51-77) and 79% were male. Twenty-two patients had pure urothelial carcinoma and 6 patients had mixed histology. Regarding clinical stage at baseline, 17 patients were T2N0, 7 were T3N0, 3 were TxN+, and 1 was T4N0.
There were 6 patients who did not undergo cystectomy; however, they were included in the intention to treat analysis. The primary end point of the study was pCR, with the goal of reaching a pCR (ypT0/isN0) rate >25% in each arm. Secondary end points for the trial were pathologic downstaging rate (<ypT2N0) and safety.
The median number of avelumab cycles received was 4.4 (range, 1-7) overall, comprising a median of 5.11 (range, 1-7) in the CG + A arm and 3.8 (range, 1-4) in the DD-MVAC arm.
Regarding safety, the most frequently reported grade 3/4 adverse events (AEs) were thrombocytopenia (25% in the CG arm vs 11% in the DD-MVAC arm), neutropenia (18% vs 4%, respectively), febrile neutropenia (4% in each arm), and creatinine increase (14% in each arm).
“Toxicity related to avelumab was relatively rare, with only one grade 3 AE (immune-related thrombocytopenia) and no patients requiring systemic steroids,” said Chanza, adding, “Importantly, no patients failed to undergo surgery due to an AE.” There also were no treatment-related deaths.
Looking ahead, Chanza said the investigators are anticipating results from a separate cohort of the AURA study that is examining avelumab-based neoadjuvant chemotherapy in cisplatin ineligible patients. These patients are being randomized to avelumab either alone or combined with gemcitabine and paclitaxel.
“Translational research and a survival analysis are also ongoing,” Chanza said in her concluding remarks.
1. Chanza NM, Carnot A, Barthelemy P, et al. Avelumab (A) as the basis of neoadjuvant chemotherapy (NAC) regimen in platinum eligible and ineligible patients (pts) with non-metastatic muscle invasive bladder cancer (NM-MIBC). 2021 ESMO Congress. September 16-21, 2021. Abstract 659MO.