Extended follow-up shows DFS benefit for pembrolizumab in MIUC

After a median 45 months of follow-up, data indicate that adjuvant pembrolizumab (Keytruda) continues to show improved disease-free survival (DFS) compared with observation in patients with high-risk muscle-invasive urothelial carcinoma.

The data, from the phase 3 A031501 AMBASSADOR trial (NCT03244384), were concurrently presented at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain and published in the New England Journal of Medicine.^1,2

Previously reported data from AMBASSADOR presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California indicated that adjuvant pembrolizumab yielded a significant improvement in DFS after a 22-month follow-up.³ At the ESMO Annual Congress, first author Andrea B. Apolo, MD presented results from a median follow-up of 45 months of the intent-to-treat population by PD-L1 expression and lymph node status.

A031501 AMBASSADOR is a phase 3 randomized, open-label, multicenter study of adjuvant pembrolizumab vs observation in patients with high-risk muscle-invasive urothelial carcinoma. Patients were randomly assigned 1:1: to receive pembrolizumab, 200 mg q3W for 1 year vs observation. Dual primary end points were DFS and overall survival (OS).

A total of 702 patients were enrolled. Enrollment was closed early due to FDA approval of nivolumab (Opdivo) for the treatment of high-risk muscle-invasive urothelial carcinoma after surgery.

Andrea B. Apolo, MD

“34% of the patients in the observation and 20% of patients in the pembrolizumab arm received a non-protocol checkpoint inhibitor or withdrew consent,” noted Apolo, medical oncologist at the National Cancer Institute of the National Institute of Health in Bethesda, Maryland.

“The final analysis of the OS data has not been performed since only 80% of the events have been reached and the efficacy boundary was not crossed at the interim analysis,” noted the authors.

Discussing baseline characteristics, Apolo noted that approximately 50% of patients in the pembrolizumab arm had lymph node-positive disease, 57.3% were PD-L1 positive, and 22.9% of patients had upper tract urothelial carcinoma.

At a median follow-up of 44.8 months (range, 0.03-70.1 months), median DFS in the pembrolizumab arm was 29.6 months (95% CI, 20.0-40.7) vs 14.2 months in the observation arm (95% CI, 11.0-20.2). The HR was 0.73 (95% CI, 0.59-0.90, P = .0027).

In patients who were PD-L1-positive, median DFS was 36.9 months in the pembrolizumab arm (95% CI, 27.2-not reached) vs 21.0 months in the observation arm (95% CI, 13.6-53.3). In patients who were PD-L1-negative, median DFS was 22.1 months in the pembrolizumab arm (95% CI, 13.2-32) vs 9.0 months in the observation arm (95% CI, 6.9-15.3).

In her concluding remarks, Apolo said, “Adjuvant pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in disease-free survival vs observation in this extended 45-month follow-up. The subgroup analysis showed that there DFS benefit with pembrolizumab in the subgroups regardless of PD-L1 expression and lymph node status and that common sites of recurrences included lymph nodes, lung, bone and liver. Based on the doubling of the median disease-free survival and the previously presented manageable toxicity, this trial supports adjuvant pembrolizumab as a therapeutic option in patients with high-risk muscle-invasive urothelial carcinoma.”

REFERENCES

1. Apolo AB, Ballman KV, Sonpavde G, et al. Alliance A031501: AMBASSADOR Study of Adjuvant Pembrolizumab (Pembro) in Muscle-Invasive Urothelial Carcinoma (MIUC) vs Observation (Obs): Extended follow-up disease-free survival (DFS) results and metastatic (met) disease recurrence distribution. Presented at: 2024 European Society for Medical Oncology Annual Congress. September 13-17, 2024. Barcelona, Spain. Abstract 1964MO. https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/session/calendar?q=1964MO

2. Apolo AB, Ballman KV, Sonpavde G, et al. Adjuvant pembrolizumab versus observation in muscle-invasive urothelial carcinoma. N Engl J Med. Published online September 15, 2024. Accessed September 15, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2401726

3. Apolo AB, Ballman KV, Sonpavde GP, et al. AMBASSADOR Alliance A031501: Phase III randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma (MIUC) vs observation. J Clin Oncol. 2024;42(suppl_4). doi:10.1200/JCO.2024.42.4_suppl.LBA531