Disitamab vedotin, an antibody–drug conjugate (ADC) targeting HER2, combined with a PD-L2 inhibitor, was superior to chemotherapy in this patient population, with a median progression-free survival (PFS) of 13 months versus 6.5 months. The safety profile was also more favorable compared with the chemotherapy arm. The study included patients with HER2-low disease.
Small testing size, but still with high overall response rate (32%) with progression-free survival of 5.6 months. Now, this is not randomized and is after failure of check point inhibitors. Of note this medication will not be marketed for second line therapy since it did not show overall survival advantage.
Both medications are approved as a single agent in second-filine therapy, and now the combination seems to be promising with manageable toxicity. Overall Response Rate (ORR): 41% I think we need phase 3 data to show superiority over single agent therapy. And now with pembrolizumab used in first-line therapy, this regimen may disappear.
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.
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.
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.