Neoadjuvant Atezolizumab Associated With High DFS in Muscle-Invasive Bladder Cancer

By Cecilia Brown - August 15, 2022

The multicenter, single-arm, phase 2 trial was conducted by Bernadett Szabados, MD, of the Queen Mary University of London and University College London Hospitals National Health Center Foundation Trust, and colleagues.

The results were published in European Urology.

The trial assessed the use of atezolizumab, a monoclonal antibody directed at the programmed cell death-ligand 1 (PD-L1) protein, in patients with muscle-invasive bladder cancer who were ineligible for or refused neoadjuvant cisplatin-based chemotherapy (n = 95). The median patient age was 73 years.

Patients received two 21-day cycles of atezolizumab 1200 mg prior to radical cystectomy. All patients received at least one cycle of atezolizumab, and 87 patients underwent radical cystectomy. The median follow-up was 25 months.

Survival Rates and Associated Factors

A pathological complete response was reported in 31% of all patients and 37% of patients who were positive for PD-L1.

The 2-year overall survival (OS) was 77% (95% CI, 68-85) and the 2-year DFS was 68% (95% CI, 58-76). The 2-year DFS in patients who achieved pathological complete response was 85% (95% CI, 65-94).

A higher T-stage (T3-T4) at baseline was significantly associated with poorer DFS (hazard ratio [HR], 2.4; 95% CI, 1.0-5.6; P=.045) as was a higher T-stage at cystectomy (HR, 13; 95% CI, 3.7-43; P<.001). Node-positive disease at surgery was also significantly associated with poorer DFS (HR, 6.6; 95% CI, 2.4-18; P<.001).

Relapse-free survival (RFS) was significantly associated with high baseline stromal CD8+ (HR, 0.25; 95% CI, 0.09-0.68; P=.007) and high post-treatment fibroblast activation protein (HR, 4.1; 95% CI, 1.3-13; P=.01).

Baseline PD-L1 levels were not significantly correlated with RFS (HR, 0.60; 95% CI, 0.24-1.5, P=.26). Tumor mutational burden at baseline also did not significantly correlate with RFS (HR, 0.72; 95% CI, 0.31-1.7; P=.46).

Circulating tumor DNA was reported in 63% of patients at baseline, in 47% of patients after neoadjuvant therapy and in 14% of patients after surgery.

Conclusions, Limitations, and Future Directions

The ABACUS trial showed immunotherapy with neoadjuvant atezolizumab was associated with higher DFS in cisplatin-ineligible patients than has been reported in clinical trials evaluating upfront radical cystectomy, which is standard treatment for those patients.

“We showed that bladder cancer patients receiving immunotherapy followed by cystectomy have good long-term outcomes,” Dr. Szabados and colleagues wrote. “Furthermore, we found that certain biological features can predict patients who might have particular benefit from this therapy.”

Randomized neoadjuvant trials that use immune checkpoint inhibitors are ongoing and “supported by these data,” according to the authors.

The lack of comparison group and randomization in the study were weaknesses, as was the exploratory nature of the biomarker analysis.

However, circulating tumor DNA positivity values were “highly prognostic at all time points” and data from the serial circulating tumor DNA analysis “may inform the development of personalized therapy in the future,” the investigators wrote.

Reference

Final results of neoadjuvant atezolizumab in cisplatin-ineligible patients with muscle-invasive urothelial cancer of the bladder

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