A very compelling option to keep an eye out for as larger studies are sure to come in the future. EV + pembrolizumab had an ORR of ~65% with durable responses. The combo arm had unsurprisingly higher grade 3-4 AE’s. For platinum-ineligible patients, it would be worth considering this regimen even today.
Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.
In Cohort K of the EV-103 phase Ib/II study, cisplatin-ineligible patients with previously untreated la/mUC were randomly assigned 1:1 to receive EV as monotherapy or in combination with Pembro. The primary end point was confirmed objective response rate (cORR) per blinded independent central review. Secondary end points included duration of response (DOR) and safety. There were no formal statistical comparisons between treatment arms.
The cORR was 64.5% (95% CI, 52.7 to 75.1) and 45.2% (95% CI, 33.5 to 57.3) for patients treated with EV + Pembro (N = 76) and EV monotherapy (N = 73), respectively. The median DOR was not reached for the combination and was 13.2 months for monotherapy; 65.4% and 56.3% of patients who responded to the combination and monotherapy, respectively, maintained a response at 12 months. The most common grade 3 or higher treatment-related adverse events (TRAEs) in patients treated with the combination were maculopapular rash (17.1%), fatigue (9.2%), and neutropenia (9.2%). EV TRAEs of special interest (any grade) in the combination arm included skin reactions (67.1%) and peripheral neuropathy (60.5%).
EV + Pembro showed a high cORR with durable responses as 1L treatment in cisplatin-ineligible patients with la/mUC. Patients who received EV monotherapy had a response and safety profile consistent with previous studies. Adverse events for EV + Pembro were manageable, with no new safety signals observed.
This antibody doublet is essentially the new SOC in met-urothelial cancer. The anti-PD1 and ADC combination is compelling in many ways and the survival outcomes compared to chemo were very significant. This combination is on NCCN, as well.
This is a negative study looking at atezolizumab + chemo vs. chemo alone in metastatic urothelial carcinoma. In the same issue, there is a negative study on atezolizumab vs. chemo alone, as well. It does seem that atezolizumab has limited disease activity versus some comparable agents.
Erdafatinib was compared to chemo in the >=2nd line in patients who had FGFR2/3 mutations, fusions or alterations with metastatic bladder cancer. Survival endpoints were superior in the targeted group with a overall survival of 12 vs. eight months. In my experience, the challenge with this group of targeted agents is tolerability.
For metastatic urothelial carcinoma, the combination of nivolumab + gemcitabine (gem) /cisplatin (cis) resulted in an improved overall response rate (ORR) of 58 vs. 43%, progression-free survival (PFS) at 12 months of 34 vs. 22% and higher rates of complete response (CR) at 22 vs. 12%. This is the first study to improve upon the chemotherapy doublet of gem/cis in this disease setting. While an interesting treatment option, this has not yet made it into the NCCN guidelines and pembrolizumab + enfortumab seems to be a better tolerated, non-chemo option that is gaining traction.
Impressive response rates and complete response in this setting, with moderate toxicities. Randomized trial is necessary to document survival, PFS differences. Cost will be very considerable in the setting value-based strategies. The clinical benefit must be quite superior in a randomized setting.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
