Adding durvalumab to chemotherapy extends survival in MIBC

Topline data from the phase 3 NIAGARA trial (NCT03732677) showed that the combination of durvalumab (Imfinzi) plus chemotherapy significantly improved event-free survival (EFS) and overall survival (OS) vs neoadjuvant chemotherapy alone in patients with muscle-invasive bladder cancer (MIBC), AstraZeneca announced in a news release.¹

The co-primary end points for the study are EFS and the pathologic complete response rate.

“Nearly half of patients with muscle-invasive bladder cancer who receive standard of care still experience disease recurrence or progression,” said trial investigator Thomas Powles, MD, professor and director of Barts Cancer Centre (QMUL) in London, UK, in a news release on the findings.¹ “These NIAGARA data show for the first time that adding durvalumab to chemotherapy before surgery followed by durvalumab extends patients’ lives.”

Regarding safety, durvalumab was generally well-tolerated in the trial, and no new safety signals emerged in either the adjuvant or neoadjuvant setting. Patients in the treatment arm did not experience a higher treatment discontinuation rate due to adverse events compared with the patients receiving chemotherapy alone. The addition of durvalumab also was not shown to compromise patients’ ability to complete surgery.

According to the news release, data from the NIAGARA trial will be presented at an upcoming medical meeting and shared with global regulatory authorities.

Overall, the open-label, multicenter NIAGARA trial is evaluating the safety and efficacy of durvalumab before and after radical cystectomy in patients with MIBC.

In total, the trial enrolled 1063 adult patients across 192 clinical trial sites in 22 countries in North America, South America, Europe, Australia, and Asia. Those included in the trial were randomly assigned to receive durvalumab plus neoadjuvant chemotherapy (gemcitabine plus cisplatin), followed by durvalumab monotherapy or to chemotherapy alone prior to cystectomy.

To be eligible for the study, patients needed to have resectable MIBC with stage T2-T4aN0/1M0 and transitional and mixed transitional cell histology, an ECOG performance status of 0 or 1, and a life expectancy of at least 12 weeks. Patients who received prior systemic chemotherapy or immunotherapy for MIBC were not eligible for inclusion.²

The co-primary end points for the study are EFS and the pathologic complete response rate. The trial’s key secondary end points are OS and safety. Additional secondary end points for the trial include metastasis-free survival, disease-free survival, and the proportion of patients who undergo cystectomy.

Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, added in the news release,¹ “The NIAGARA results support our strategy to move immunotherapy to the early stages of cancer treatment. This perioperative regimen with IMFINZI improved survival and reduced the rate at which patients experience disease recurrence or progression. We are eager to bring this regimen with the potential to transform the standard of care to patients as soon as possible.”

In addition to the NIAGARA trial, durvalumab is also being assessed in multiple phase 3 trials across different stages of bladder cancer, including the POTOMAC trial (NCT03528694) in non-MIBC, the VOLGA trial (NCT04960709) in patients with MIBC who are cisplatin-ineligible or refuse cisplatin, and the NILE trial (NCT03682068) in patients with locally advanced or metastatic bladder cancer.

Durvalumab is currently approved across indications in non-small cell lung cancer, biliary tract cancer, unresectable hepatocellular carcinoma, and advanced or recurrent mismatch repair deficient endometrial cancer.

References

1. IMFINZI (durvalumab) demonstrated statistically significant and clinically meaningful improvement in event-free survival and overall survival for muscle-invasive bladder cancer in NIAGARA Phase III trial. News release. AstraZeneca. Published online and accessed June 25, 2024. https://www.astrazeneca-us.com/media/press-releases/2024/imfinzi-durvalumab-demonstrated-statistically-significant-and-clinically-meaningful-improvement-in-event-free-survival-and-overall-survival-for-muscle-invasive-bladder-cancer-in-niagara-phase-iii-trial.html

2. Durvalumab+ gemcitabine/cisplatin (neoadjuvant treatment) and durvalumab (adjuvant treatment) in patients with MIBC (NIAGARA). ClinicalTrials.gov. Last updated March 18, 2024. Accessed June 25, 2024. https://clinicaltrials.gov/study/NCT03732677