Neoadjuvant chemo-immunotherapy leads to downstaging in muscle-invasive urothelial cancer
Click Here to Manage Email Alerts
SAN FRANCISCO — Neoadjuvant chemo-immunotherapy led to significant downstaging prior to definitive surgery for patients with muscle-invasive urothelial cancer, according to data presented at ASCO Genitourinary Cancers Symposium.
Researchers observed this outcome among both cisplatin-eligible and cisplatin-ineligible patients.
“It’s exciting that we were able to not just meet but quite exceed ... the null hypothesis,” researcher Jason Brown, MD, PhD, genitourinary medical oncologist with University Hospitals, told Healio.
Background and methodology
Immune checkpoint inhibition is standard therapy for patients with metastatic urothelial carcinoma; however, its role in muscle-invasive disease has not been clearly defined.
Prior studies have demonstrated promising antitumor activity of neoadjuvant immune checkpoint inhibition, according to study background.
Brown and colleagues conducted the phase 1B/phase 2 HCRN GU14-188 study to assess neoadjuvant chemo-immunotherapy for patients with cisplatin-eligible or cisplatin-ineligible muscle-invasive urothelial cancer.
Researchers enrolled 81 patients with clinical stage T2-4aN0M0 urothelial cancer. The cohort included 43 cisplatin-eligible patients (median age, 64 years; range, 42-77; 73.8% men; 83.3% white) and 38 cisplatin-ineligible patients (median age, 73 years; range, 58-83; 71.8% men; 92.3% white).
All patients received neoadjuvant pembrolizumab (Keytruda, Merck) dosed at 200 every 3 weeks for five cycles.
Cisplatin-eligible patients received four 21-day cycles of gemcitabine (1,000 mg/m2 on days 1 and 8) with cisplatin (70 mg/m2 on day 1, or 35 mg/m2 on days 1 and 8).
Cisplatin-ineligible patients received three 28-day cycles of gemcitabine (1,000 mg/m2 on days 1, 8 and 15).
Patients then underwent definitive surgery.
Investigator-assessed pathologic muscle-invasive response rate ( ypT1N0) assessed at surgery served as the primary endpoint. Researchers established a null hypothesis for rates of 23% in the cisplatin-eligible group and 18% in the cisplatin-ineligible group.
Pathologic complete response, 18-month RFS, 36-month OS and definitive surgery rate served as secondary endpoints.
Results
Median follow-up was 54.8 months (range, 2.2-67) for the cisplatin-eligible cohort and 29.2 months (range 1.5-62.6) for the cisplatin-ineligible cohort.
Both cohorts surpassed the null hypothesis for the primary endpoint.
Researchers reported pathologic muscle-invasive response rates of 61% (95% CI, 45-75) in the cisplatin-eligible group and 52% (95% CI, 35-68) in the cisplatin-ineligible group.
Among cisplatin-eligible patients, researchers reported a pathologic complete response rate of 44% (95% CI, 29-61), a definitive surgery rate of 88% (95% CI, 72-93), an 18-month RFS rate of 82% (95% CI, 66-91) and a 36-month OS rate of 79% (95% CI, 65-90).
Among cisplatin-ineligible patients, researchers reported a pathologic complete response rate of 45% (95% CI, 31-61), a definitive surgery rate of 87% (95% CI, 73-94), an 18-month RFS rate of 65% (95% CI, 48-78) and a 36-month OS rate of 66% (95% CI, 47-79).
In the overall cohort, the most common grade 3 or higher toxicities included anemia (29.6%), hypertension (28.3%) and neutropenia (24.7%). One patient in the cisplatin-eligible cohort died of postoperative sepsis.
Grade 3 or higher immune-related adverse events included elevated liver enzymes (3.7%), rash (2.5%), pneumonitis (2.5%) and colitis (2.5%).
Next steps
Researchers are continuing their analysis in hopes of identifying biomarkers for response.
“We need to wait for the survival data to completely mature,” Brown told Healio. “Median follow-up ... [in] cohort A was 54.8 months while cohort B patients were enrolled a little bit later, so it’s still only at 29 months. But that tail at the end of the curve is quite encouraging — patients seem to have a durable response to this treatment.
“The cisplatin-ineligible cohort needs to be explored a little bit further,” Brown added. “The other thing to look into is other novel technology [for] measuring response. ... There are a lot of avenues to look forward to in this field.”
Collapse
Brown J, et al. Abstract 448. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 16-18, 2023; San Francisco.
Click Here to Manage Email Alerts