Phillip Palmbos, MD, PhD, assistant professor, University of Michigan Health, discusses the utilization of adjuvant nivolumab (Opdivo) following cystectomy in high-risk, muscle-invasive bladder cancer. 

The randomized phase 3 CheckMate 274 trial (NCT02632409) examined nivolumab vs placebo in this patient population, Palmbos says. High-risk patients in this trial were defined as those with node-positive disease at cystectomy, T2 or greater for patients who underwent prior neoadjuvant chemotherapy, or T3 or greater with no history of neoadjuvant chemotherapy, Palmbos adds. 

The primary end point of disease-free survival was met, particularly in the in the PD-L1–positive population, Palmbos adds. For patients with high-risk features observed in the CheckMate 274 study, nivolumab could have a role in the adjuvant setting following cystectomy, Palmbos concludes.

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Phillip Palmbos, MD, PhD, discusses the utilization of adjuvant nivolumab following cystectomy in high-risk, muscle-invasive bladder cancer. 


 Dr. Palmbos on the Utilization of Nivolumab Following Cystectomy in Muscle-Invasive Bladder Cancer

Phillip L. Palmbos, MD, PhD, assistant professor, Rogel Cancer Center, University of Michigan Health, Michigan Medicine, discusses remaining questions in metastatic urothelial carcinoma.

Although the prespecified overall survival end point was not met in the phase 3 IMvigor130 (NCT02807636) or KEYNOTE-361 (NCT02853305) trials, the positive trends toward a survival advantage with immunotherapy-containing regimens suggest chemoimmunotherapy could have utility for patients with metastatic urothelial carcinoma, Palmbos says. However, biomarkers need to be identified to inform which patients are likely to respond to immunotherapy. 

Additionally, the efficacy observed with enfortumab vedotin-ejfv (Padcev) and sacituzumab govitecan-hziy (Trodelvy) suggests that antibody-drug conjugates could have utility alone or in combination with chemotherapy in earlier-stage settings for patients with metastatic disease, Palmbos explains.

Neoadjuvant treatment with immunotherapy and other novel agents is the subject of ongoing research, Palmbos says. The ongoing phase 3 NIAGARA (NCT03732677) and KEYNOTE-866 (NCT03924856) trials are attempting to answer the open question of whether chemoimmunotherapy has a role as neoadjuvant treatment for patients with bladder cancer. 

Finally, optimizing treatment for patients with high-risk muscle-invasive disease who didn’t receive prior neoadjuvant chemotherapy remains an area of unmet need, Palmbos explains. These patients may be best suited for cisplatin-based neoadjuvant chemotherapy or adjuvant nivolumab (Opdivo); however, data are not yet conclusive as to the optimal approach, Palmbos concludes.

Phillip L. Palmbos, MD, PhD, discusses remaining questions in metastatic urothelial carcinoma.  



Dr. Palmbos on Remaining Questions in Metastatic Urothelial Carcinoma 

Phillip Palmbos, MD, PhD, assistant professor, University of Michigan Health, discusses the role of chemoimmunotherapy in patients with bladder cancer.

The phase 3 JAVELIN Bladder 100 trial (NCT02603432), which examined avelumab (Bavencio) in patients with locally advanced or metastatic urothelial cancer, established a survival benefit with the agent in the maintenance setting following first-line chemotherapy. Based on these findings, patients with stable or ongoing disease response after frontline cisplatin-based chemotherapy should be considered for treatment with the drug, according to Palmbos. These data provide insight into optimal sequencing and utilization of immune checkpoint inhibitors in this disease, Palmbos says.

However, chemoimmunotherapy still cannot be recommended for patients with metastatic bladder cancer, Palmbos continues. The phase 3 IMvigor130 trial (NCT02807636), which examined the addition of atezolizumab (Tecentriq) to platinum-based chemotherapy, showed an improved disease-free survival in patients with advanced or metastatic urothelial carcinoma, but did not demonstrate an improvement in overall survival, Palmbos explains. This was also the case when pembrolizumab (Keytruda) was combined with chemotherapy in the phase 3 KEYNOTE-361 trial (NCT02853305), Palmbos adds.

Although ongoing studies may provide more clarity on how chemoimmunotherapy regimens can be used in the treatment of this patient population, the approach does not currently have a clear role in this disease, Palmbos concludes. 

Phillip Palmbos, MD, PhD, discusses the role of chemoimmunotherapy in patients with bladder cancer.

Dr. Palmbos on the Role of Chemoimmunotherapy in Bladder Cancer 

Phillip Palmbos, MD, PhD, assistant professor, University of Michigan Health, discusses updates and therapeutic recommendations for the frontline treatment of patients with bladder cancer.

Significant progress has been made in the treatment of this patient population over the past several years, with novel, effective agents becoming available, such as immune checkpoint inhibitors and antibody-drug conjugates, according to Palmbos. For patients with metastatic disease in the frontline setting, those who are eligible should still receive cisplatin-based chemotherapy, Palmbos says.

Additionally, these patients can also move directly on to receive maintenance therapy with immune checkpoint inhibitors, based on findings from the phase 3 JAVELIN Bladder 100 trial (NCT02603432), Palmbos adds.

There is opportunity for the use of adjuvant immunotherapy in eligible patients who have high-risk features after cystectomy, particularly those who are not candidates for adjuvant chemotherapy, Palmbos explains. These are positive developments that are applicable for the bladder cancer community, Palmbos concludes.

Phillip Palmbos, MD, PhD, discusses updates and therapeutic recommendations for the frontline treatment of patients with bladder cancer.

Phillip Palmbos, MD, PhD

Articles

Dr. Palmbos on the Utilization of Nivolumab Following Cystectomy in Muscle-Invasive Bladder Cancer

Dr. Palmbos on Remaining Questions in Metastatic Urothelial Carcinoma

Dr. Palmbos on the Role of Chemoimmunotherapy in Bladder Cancer

Dr. Palmbos on Frontline Treatment Recommendations in Bladder Cancer