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.
Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2–directed antibody-drug conjugate with US Food and Drug Administration–accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3.
TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label phase II study. Patients were CPI-naïve and had mUC progression after platinum-based chemotherapy in the metastatic setting or ≤12 months in the (neo)adjuvant setting. Patients received 10 mg/kg of SG once on days 1 and 8 and 200 mg of pembrolizumab once on day 1 of 21-day cycles. The primary end point was objective response rate (ORR) per central review. Secondary end points included clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS) per central review, and safety.
Cohort 3 included 41 patients (median age 67 years; 83% male; 78% visceral metastases [29% liver]). With a median follow-up of 14.8 months, the ORR was 41% (95% CI, 26.3 to 57.9; 20% complete response rate), CBR was 46% (95% CI, 30.7 to 62.6), median DOR was 11.1 months (95% CI, 4.8 to not estimable [NE]), and median PFS was 5.3 months (95% CI, 3.4 to 10.2). The median overall survival was 12.7 months (range, 10.7-NE). Grade ≥3 treatment-related adverse events occurred in 61% of patients; most common were neutropenia (37%), leukopenia (20%), and diarrhea (20%).
SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of SG plus CPI in mUC.
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.
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