The ESMO 2024 congress featured several presentations that could reshape the treatment landscape for kidney and bladder cancers. Key studies challenged existing paradigms and introduced potential new standards of care.
Kidney Cancer: Challenging the Status Quo
Ignacio Durán highlighted two studies that are challenging the current management of metastatic renal cell carcinoma (mRCC). The first, TiNivo-2, explored the efficacy of adding a checkpoint inhibitor after prior checkpoint inhibitor treatment. In this study, patients with advanced kidney cancer who had progressed on checkpoint inhibitor-based therapy were randomized to receive either nivolumab plus tivozanib or tivozanib alone. The results indicated no benefit in progression-free survival or overall survival with the combination, suggesting that sequencing checkpoint inhibitors is not beneficial in this setting. "The study did not show any benefit in the primary endpoint that was the progression-free survival, but it did not demonstrate any benefit also in overall survival," said Durán. This reinforces the use of tyrosine kinase inhibitors (TKIs) as monotherapy upon progression after checkpoint inhibitor treatment.
The SUNNIFORECAST trial addressed the non-clear cell RCC subgroup, where treatment evidence is limited. This study compared ipilimumab plus nivolumab to TKI therapy in patients with advanced non-clear cell renal cell carcinoma. The ipilimumab-nivolumab combination demonstrated a superior overall survival rate at 12 months (86% vs. 76%, p<0.05) and improved overall response rates. "When we look at these data, I think these challenge the current standard of care in non-clear cell and it generates a new option for IPI-NIVO," Durán noted. While further analysis is needed, these results suggest a potential new treatment option for this challenging patient population.
Data from the LITESPARK-005 study, which evaluated belzutifan in advanced kidney cancer after progression on one to three prior systemic regimens, showed no overall survival benefit despite a previously reported progression-free survival benefit. This raises questions about the optimal setting for belzutifan use.
Bladder Cancer: Refining Perioperative Treatment
In bladder cancer, three studies presented at ESMO 2024 are poised to influence clinical practice. The SunRISe-4 trial is investigating an alternative to cisplatin-based neoadjuvant chemotherapy for patients unfit to receive cisplatin. This trial uses the TAR-200 intravesical device, which releases gemcitabine continuously, in combination with the checkpoint inhibitor cetrelimab. Preliminary results showed a pathological complete response (Path-CR) rate of 42% with the combination. "I think we can say that we've got another potential approach for patients with muscle-invasive bladder cancer who were not good enough to receive cisplatin-based chemotherapy," Durán commented.
The TOMBOLA study, an academic trial from Denmark, explored the role of circulating tumor DNA (ctDNA) in selecting patients for adjuvant immunotherapy after cystectomy. Early data suggest that ctDNA negativity after radical cystectomy is associated with a very low relapse rate, indicating that ctDNA monitoring may help identify patients who would benefit most from adjuvant therapy.
The NIAGARA study, a global phase III trial, evaluated perioperative durvalumab combined with neoadjuvant chemotherapy in cisplatin-eligible patients with muscle-invasive bladder cancer. Patients were randomized to receive either cisplatin plus gemcitabine followed by cystectomy or cisplatin plus gemcitabine plus durvalumab followed by cystectomy and adjuvant durvalumab. The study demonstrated a statistically significant and clinically meaningful improvement in event-free survival and overall survival in the durvalumab arm, along with a superior Path-CR rate. "The use of neoadjuvant chemotherapy plus durvalumab by adjuvant durvalumab has demonstrated an improvement in event-free survival and overall survival when compared with chemotherapy alone and could represent a new standard of care in this setting," Durán concluded.
These studies collectively highlight the evolving treatment strategies for kidney and bladder cancers, emphasizing the importance of personalized approaches and novel therapeutic combinations.
