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ASCO 2024

ASCO 2024: Avelumab as Neoadjuvant Therapy in Patients with Muscle-Invasive Urothelial Carcinoma: Survival Data of AURA Trial, Oncodistinct 004

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 31st and June 4th, 2024 was host to a kidney and bladder rapid oral abstract session. Dr. Jeremy Blanc presented the survival analysis of the AURA trial evaluating avelumab as neoadjuvant therapy in patients with muscle-invasive urothelial carcinoma.


Cisplatin-based neoadjuvant chemotherapy followed by surgery is the standard of care approach for patients with clinically localized (cT2-4aN0M0) muscle-invasive urothelial carcinoma of the bladder. However, it is estimated that nearly half of such patients are unfit for cisplatin-based chemotherapy with no alternative systemic therapy currently approved in the neoadjuvant setting. Neoadjuvant studies investigating immune checkpoint inhibitors (ICI) have demonstrated promising anti-tumor activity and survival outcomes:

  • ICI single agent : pCR= 29–46%, >85% overall survival at three years1-3
  • ICI plus chemotherapy : pCR= 33–43%, >81% overall survival at three years4-5

AURA is a multi-center, non-comparative randomized phase II trial investigating neoadjuvant avelumab alone or in combination with chemotherapy. Patients with muscle-invasive urothelial carcinoma of the bladder planned for a radical cystectomy + pelvic lymphadenectomy were randomized by cisplatin eligibility to neoadjuvant therapy as follows:

  • Cisplatin-eligible (Cohort 1):
    • Gemcitabine/cisplatin + avelumab
    • Dose-dense MVAC + avelumab
  • Cisplatin-ineligible + avelumab:
    • Paclitaxel/gemcitabine + avelumab
    • Avelumab monotherapy

The primary endpoint is the proportion of patients achieving a complete pathologic response (i.e., ypT0/TisN0). Secondary endpoints include:

  • Proportion of patients achieving <ypT2N0
  • Safety (CTCAE v4)
  • Event-free survival (EFS) and overall survival at 12 and 36 months


In the cisplatin-eligible cohort of patients, a pathologic complete response was observed in 22/38 (58%) patients in the ddMVAC + avelumab arm and 19/35 (54%) patients in the gemcitabine/cisplatin + avelumab arm. The 12-month EFS rates were 92% in the ddMVAC + avelumab arm, compared to 84% for gemcitabine/cisplatin + avelumab. The preliminary 36-month EFS rates were 79% and 62%, respectively. For overall survival, the 12 months rates were slightly higher in favor of ddMVAC + avelumab (95% versus 92%) and considerably higher at 36 months in favor of ddMVAC + avelumab (85% versus 64%).survival, the 12 months rates were slightly higher in favor of ddMVAC + avelumab (95% versus 92%) and considerably higher at 36 months in favor of ddMVAC + avelumab (85% versus 64%)
Patients with a pathologic complete response experienced significantly better overall survival outcomes, confirming the prognostic significance of this pathologic endpoint.overall survival outcomes, confirming the prognostic significance of this pathologic endpoint.
In the cisplatin-ineligible cohort, a pathologic complete response was observed in 4/28 (14%) and 9/27 (33%) patients in the paclitaxel/gemcitabine + avelumab and avelumab monotherapy arms, respectively. The event-free and overall survival rates were similar between the two arms: complete response was observed in 4/28 (14%) and 9/27 (33%) patients in the paclitaxel/gemcitabine + avelumab and avelumab monotherapy arms, respectivelyevent-free and overall survival rates were similar between the two arms:
Dr. Blanc concluded as follows:

  • Cisplatin-eligible cohort :
    • High event-free and overall survival rates are achieved at 12 months and 36 months in patients treated with neoadjuvant avelumab in combination with cisplatin-based chemotherapies, especially in patients treated with ddMVAC + avelumab.
  • Cisplatin-ineligible cohort :
    • Lower survival outcomes are achieved at 12 months, with no additional benefit from addition of avelumab to paclitaxel/gemcitabine.
    • Longer follow-up is needed for a 36-month survival analysis.
  • Achieving a complete pathologic response is correlated with better survival outcomes for each treatment arm.
  • Further investigation through phase III trials is essential to validate these findings including biomarker identification for optimizing muscle-invasive bladder cancer care and patient selection.

Presented By: Jeremy Blanc, MD, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles, Brussels, Belgium

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, May 31st – June 4th, 2024 

References:
  1. Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol 2018;36(34):3353-60.
  2. Basile G, Banidin M, Gibb EA, et al. Neoadjuvant Pembrolizumab and Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Cancer: 3-Year Median Follow-Up Update of PURE-01 Trial. Clin Cancer Res 2022;28(23):5107-14.
  3. Powles T, Kockx M, Rodriguez-Vida, et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med 2019; 25(11):1706-14.
  4. Funt SA, Lattanzi M, Whiting K, et al. Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial. J Clin Oncol. 2022;40(12): 1312-22.
  5. Cathomas R, Rothschild SI, Hayoz S, et al. Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17. J Clin Oncol. 2023;41(33): 5131-9.