Key Takeaways
- TAR-200 with cetrelimab nearly doubles the pathological complete response (pCR) rate compared to cetrelimab alone in patients with muscle-invasive bladder cancer (MIBC).
- TAR-200 plus cetrelimab shows significant tumor size reduction, improving surgical outcomes and reducing recurrence risk.
- The treatment offers a potential alternative for patients ineligible for or refusing platinum-based chemotherapy.
Johnson & Johnson has announced interim findings from the ongoing Phase 2 SunRISe-4 study, revealing that TAR-200 combined with cetrelimab (CET) nearly doubles the pathological complete response (pCR) rate compared to CET alone in patients with muscle-invasive bladder cancer (MIBC). For patients who are ineligible for or refuse neoadjuvant platinum-based chemotherapy and are scheduled for radical cystectomy (RC), this combination therapy offers new hope for better outcomes. These results, presented at the European Society of Medical Oncology (ESMO) 2024 Congress, mark a significant step forward in treating this aggressive form of bladder cancer.
The study shows that neoadjuvant treatment with TAR-200 plus CET achieved a pCR rate of 42% compared to 23% with CET alone, representing a nearly twofold increase in response. This improvement is especially significant for patients with histologically proven, non-metastatic MIBC. The pathological overall response (pOR) rate, defined as the proportion of patients with ≤ pT1 stage tumors, was also considerably higher at 60% for the combination treatment, compared to 36% for CET alone. These findings suggest that combining TAR-200 with cetrelimab could be key in improving bladder cancer treatment outcomes.
Enhanced Response and Tumor Reduction in Bladder Cancer Patients
In a subgroup analysis of patients with organ-confined bladder cancer (cT2), TAR-200 plus CET once again outperformed CET alone. The pCR rate for these patients was 48%, compared to 23% for those receiving CET only. Additionally, 68% of patients treated with TAR-200 plus CET were downstaged to ≤ pT1 at the time of radical cystectomy. This downstaging is critical as it improves the likelihood of better surgical outcomes and reduces the risk of recurrence, a significant concern for patients with muscle-invasive bladder cancer.
The ability to reduce tumor size prior to surgery can be crucial in improving the chances of successful surgery and potentially lowering the risk of the cancer returning post-surgery. These findings point to TAR-200 plus cetrelimab as a promising option for bladder cancer patients, particularly those who are ineligible for standard chemotherapy options, offering hope for better long-term outcomes and improved quality of life.
TAR-200 Plus Cetrelimab as a New Treatment Approach for Bladder Cancer
Muscle-invasive bladder cancer (MIBC) is an aggressive form of bladder cancer, significantly increasing the risk of metastasis and challenging to treat effectively, especially in patients who cannot undergo standard chemotherapy. Radical cystectomy (RC), which involves the removal of the bladder and nearby organs, is often the primary treatment option. However, the invasive nature of this surgery, combined with the need for urinary diversion, presents significant challenges for patients.
The investigational therapy TAR-200 offers a novel approach by providing extended local release of gemcitabine directly into the bladder, maximizing the drug’s impact on tumor cells while minimizing systemic exposure. TAR-200, combined with cetrelimab, a PD-1 inhibitor, could redefine neoadjuvant treatment for bladder cancer by enhancing local drug delivery and improving immune system response against tumor cells.
Treatment-related adverse events (TRAEs) were reported in 72% of patients treated with the TAR-200 and cetrelimab combination, compared to 44% of those receiving CET alone. Most adverse events were Grade 1 or 2, with 9% of patients discontinuing treatment due to side effects in the TAR-200 group, compared to 8% in the CET group. Importantly, no patients discontinued CET alone due to adverse events, highlighting the tolerability of the treatment.
Bladder Cancer Treatment Challenges and Innovations
Bladder cancer remains the ninth most common cancer worldwide, with muscle-invasive bladder cancer (MIBC) being one of the most severe forms. Despite advances in treatments like Bacillus Calmette-Guerin (BCG) immunotherapy, many patients—30-40%—do not respond to BCG and face disease recurrence or progression. For these patients, radical cystectomy is often the only option, but this major surgery can lead to significant complications and a reduction in quality of life due to the need for urinary diversion.
The introduction of TAR-200 offers a significant breakthrough for bladder cancer treatment. It is an investigational drug delivery system designed to release gemcitabine into the bladder over an extended period, potentially improving its therapeutic effect. TAR-200 is administered in a quick, anesthesia-free procedure, making it a less invasive treatment option. In December 2023, TAR-200 received Breakthrough Therapy Designation (BTD) from the FDA for the treatment of patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) who are unresponsive to BCG and ineligible for radical cystectomy.
These ongoing studies, including the SunRISe-4 trial, provide a growing body of evidence that TAR-200 combined with cetrelimab could be a game-changer in the fight against bladder cancer, especially for patients who have limited treatment options.
A Promising Future for Bladder Cancer Patients
The results from the SunRISe-4 study offer new hope for patients with muscle-invasive bladder cancer, particularly those who are ineligible for traditional chemotherapy. By nearly doubling the pCR rate, TAR-200 combined with cetrelimab shows great potential to improve surgical outcomes and reduce the risk of cancer recurrence, marking a significant advancement in bladder cancer treatment.
As more data emerges from ongoing trials, this combination therapy could become a new standard of care for bladder cancer patients. The investigational TAR-200 system provides a novel way to deliver gemcitabine, while cetrelimab enhances the body’s immune response to fight cancer cells. This dual approach, coupled with a favorable safety profile, positions TAR-200 plus cetrelimab as a promising option for improving outcomes in muscle-invasive bladder cancer.
Resource: Johnson & Johnson, September 16, 2024
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