The University of Chicago, Chicago, IL
Peter H. O'Donnell , Arjun Vasant Balar , Jacqueline Vuky , Daniel Castellano , Joaquim Bellmunt , Thomas Powles , Dean F. Bajorin , Petros Grivas , Noah M. Hahn , Elizabeth R. Plimack , Jin Zhi Xu , James Luke Godwin , Blanca Homet Moreno , Ronald De Wit
Background: Pembro was approvedfor cisplatin-ineligible patients with untreated advanced UC based on initial results of the phase 2 KEYNOTE-052 study (NCT02335424), which showed an ORR of 29%. Updated results after up to 5 years of follow-up are presented. Methods: KEYNOTE-052 is a single-arm, multi-site, open-label trial. Patients had advanced or metastatic UC, were cisplatin ineligible (criteria: ECOG PS 2, CrCl ≥30 to ̃60 mL/min, grade ≥2 peripheral neuropathy/hearing loss, NYHA class III heart failure), and had not previously received chemotherapy for advanced/metastatic disease. Patients received pembro 200 mg IV Q3W until progression, unacceptable toxicity, withdrawal, or 24 mo of therapy, whichever occurred first. PD-L1 status was determined by combined positive score (CPS, number of PD-L1–staining cells [tumor cells, lymphocytes, macrophages] divided by the total number of viable tumor cells, multiplied by 100); PD-L1–positive was CPS ≥10. The primary end point was confirmed ORR (RECIST v1.1, independent central review). Key secondary end points were duration of response (DOR), OS, and safety. Results: Among 370 enrolled patients, median age was 74 y, 315 (85.1%) had visceral disease, and 43 (11.6%) completed 24 mo of therapy. Median time from enrollment to data cutoff (Sep 26, 2020) was 56.3 mo (range, 51.2-65.3) for all patients and 56.0 mo (range, 51.4-65.2) for the 110 patients (29.7%) with CPS ≥10. Confirmed ORR for all patients was 28.9% (95% CI, 24.3-33.8); complete response, 9.5% (n=35); partial response, 19.5% (n=72). Median DOR was 33.4 mo (range, 1.4+ to 60.7+); 44.8% and 39.4% of patients had DOR ≥36 and ≥48 mo, (Kaplan-Meier estimates). Median OS was 11.3 mo (95% CI, 9.7-13.1); 24- and 36-mo OS rates were 31.5% and 22.1%. Patients with CPS ≥10 had better outcomes than patients with CPS <10 (Table). Treatment-related adverse events (AEs) occurred in 67.3% of patients; 21.1% of treatment-related AEs were grade ≥3, including 1 death (myositis). Conclusions: After up to 5 y of follow-up, pembro continued to elicit clinically meaningful, durable antitumor activity in cisplatin-ineligible patients with advanced UC. These effects were more pronounced in patients with CPS ≥10. Clinical trial information: NCT02335424
CPS <10 n=251 | CPS ≥10 n=110 | Total N=370 | |
---|---|---|---|
Confirmed ORR, % (95% CI) | 20.7 (15.9-26.3)a | 47.3 (37.7-57.0)a | 28.9 (24.3-33.8)b |
DOR, median (range), mo | 21.2 (1.6+ to 59.7+)a | NR (1.4+ to 60.7+)a | 33.4 (1.4+ to 60.7+)b |
DOR ≥36 months, % | 34.4 | 57.6 | 44.8 |
DOR ≥48 months, % | 27.4 | 57.6 | 39.4 |
OS, median (95% CI), mo | 9.7 (7.6-11.5) | 18.5 (12.2-28.5) | 11.3 (9.7-13.1) |
OS at 36 months, % (95% CI) | 15.4 (11.2-20.1) | 35.8 (26.9-44.7) | 22.1 (18.0-26.5) |
a52 responders. b107 responders; 3 had unknown PD-L1 status.
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