Imfinzi Perioperative Treatment Enhances Survival Outcomes in Muscle-Invasive Bladder Cancer Patients, Regardless of Pathologic Response, in NIAGARA Phase III Trial
A post-hoc exploratory analysis of the NIAGARA Phase III clinical trial has revealed that AstraZeneca’s Imfinzi (durvalumab), when used perioperatively in combination with neoadjuvant chemotherapy, significantly improves event-free survival (EFS) and overall survival (OS) in comparison to neoadjuvant chemotherapy and radical cystectomy alone. These benefits were observed in patients with muscle-invasive bladder cancer (MIBC), regardless of whether they achieved a pathologic complete response (pCR).
Patients included in the study received four cycles of Imfinzi alongside neoadjuvant chemotherapy before undergoing radical cystectomy—a surgical procedure to remove the bladder. This was followed by an additional eight cycles of Imfinzi as monotherapy.
The analysis showed that patients treated with the Imfinzi-based regimen experienced improved EFS and OS compared to those in the control group, both among those who attained pCR and those who did not.
Specifically, the treatment lowered the likelihood of disease progression, recurrence, failure to proceed with surgery, or death by 42% in patients who achieved pCR and by 23% in those who did not. Additionally, the risk of mortality was reduced by 28% in the pCR group and by 16% in non-pCR patients.
Furthermore, the regimen led to improved metastasis-free survival (MFS) and disease-specific survival (DSS), both of which were secondary endpoints of the trial. In the intent-to-treat (ITT) population, the risk of developing distant metastases or dying was reduced by 33%, while the likelihood of death specifically caused by bladder cancer was lowered by 31% compared to the control group.
As a result of these findings, the combination of perioperative Imfinzi with neoadjuvant chemotherapy was granted Priority Review in the United States in December 2024 for the treatment of MIBC patients. Regulatory submissions are also under evaluation in the European Union (EU), Japan, and multiple other countries based on the NIAGARA trial results.
Pfizer and Astellas Report Long-Term Benefits of Enfortumab Vedotin Plus Pembrolizumab for Advanced Bladder Cancer
Pfizer and Astellas have shared updated findings from a Phase 3 clinical trial, EV-302, highlighting the long-term effectiveness of combining enfortumab vedotin with pembrolizumab as a first-line treatment for patients with locally advanced or metastatic urothelial cancer (la/mUC). The results, after nearly 30 months of follow-up, show that the combination therapy significantly outperforms traditional chemotherapy, reinforcing its potential as a new standard of care for this patient population.
The trial demonstrated that the combination of enfortumab vedotin, a targeted antibody-drug conjugate, and pembrolizumab, an immune checkpoint inhibitor, doubled median overall survival (OS) and progression-free survival (PFS) compared to chemotherapy.
Specifically, the median OS was 33.8 months for the combination therapy versus 15.9 months for chemotherapy. Additionally, the risk of death was reduced by 49%, and the risk of disease progression or death was cut by 52%.
These benefits were consistent across all patient subgroups, including those eligible and ineligible for cisplatin-based treatments.
The safety profile of the combination therapy remained consistent with earlier findings, with no new safety concerns identified. Exploratory analyses also revealed that patients achieving a confirmed complete response (cCR) experienced durable benefits.
Among evaluable patients, the confirmed objective response rate (cORR) was 67.5% for the combination therapy, compared to 44.2% for chemotherapy. The median duration of response (DOR) was 23.3 months for the combination, significantly longer than the 7.0 months observed with chemotherapy. Notably, 30.4% of patients treated with the combination achieved a cCR, compared to 14.5% in the chemotherapy group.
About the EV-302 Trial
The EV-302 trial is a global, open-label, randomized Phase 3 study designed to evaluate the efficacy and safety of enfortumab vedotin combined with pembrolizumab versus standard platinum-based chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 participants, regardless of their PD-L1 status, who were eligible for cisplatin or carboplatin chemotherapy. The primary endpoints of the trial were overall survival and progression-free survival, assessed by blinded independent central review. Secondary endpoints included objective response rate, duration of response, and safety.
These findings underscore the potential of enfortumab vedotin plus pembrolizumab to transform the treatment landscape for advanced bladder cancer, offering hope to patients with limited options. Pfizer and Astellas are committed to advancing this innovative therapy and are working closely with regulatory authorities to expedite its availability to patients worldwide.
Pfizer’s Talzenna Combined with Xtandi Shows Significant Survival Benefits in Metastatic Castration-Resistant Prostate Cancer
Pfizer has announced groundbreaking results from its Phase 3 TALAPRO-2 study, revealing that the combination of Talzenna (talazoparib), a PARP inhibitor, and Xtandi (enzalutamide), an androgen receptor pathway inhibitor (ARPI), significantly improves overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). This marks the first time a PARP inhibitor and ARPI combination has demonstrated statistically significant and clinically meaningful survival benefits, regardless of homologous recombination repair (HRR) gene mutation status.
The study, which included both unselected patients (Cohort 1) and those with HRR gene mutations (Cohort 2), showed substantial improvements in median overall survival. In Cohort 1, the combination therapy extended median OS by nearly 9 months compared to Xtandi alone (45.8 months vs. 37.0 months), representing a 20% reduction in the risk of death. For patients with HRR mutations in Cohort 2, the improvement was even more pronounced, with a 14-month increase in median OS (45.1 months vs. 31.1 months) and a 38% reduction in the risk of death. These results were consistent across patients with both BRCA and non-BRCA gene alterations.
The study also confirmed that the clinical benefits observed in earlier analyses, including radiographic progression-free survival (rPFS) and other secondary endpoints, were maintained over time. The safety profile of the combination therapy was consistent with the known effects of each drug, with manageable side effects such as anemia, neutropenia, and fatigue. Dose adjustments and supportive care were effective in addressing these adverse events.
About Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Prostate cancer is the second most common cancer in men globally and the fifth leading cause of cancer-related deaths among men, with approximately 1.4 million new cases diagnosed in 2022. In the U.S., it is the most frequently diagnosed cancer in men. mCRPC is an advanced form of prostate cancer that has spread beyond the prostate gland and no longer responds to treatments that lower testosterone levels. It is estimated that 10–20% of prostate cancer patients develop mCRPC within 5–7 years of diagnosis, and 1.2–2.1% of all prostate cancer cases worldwide are classified as mCRPC.
Pfizer’s findings from the TALAPRO-2 study represent a significant step forward in addressing the unmet needs of mCRPC patients. The company plans to engage with regulatory authorities to explore approval pathways for this combination therapy, offering hope for improved outcomes for patients battling this aggressive form of cancer.
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