(UroToday.com) Ozgur Ozyilkan presented an analysis of the KEYNOTE-361 data, with a specific focus on outcomes in patients who had a complete response to first-line pembrolizumab or platinum-based chemotherapy in advanced urothelial carcinoma (UC).
The basis of this analysis was the landmark phase 3 randomized, open-label KEYNOTE-361 (NCT02853305) study, in which patients with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma were randomized to pembrolizumab ± chemotherapy versus chemotherapy in the first line setting. Ultimately, the trial did not meet its prespecified endpoints.
The authors note that 15% in the Pembro+chemo arm, 11% in the pembro monotherapy arm and 12% in the chemotherapy arm had a complete response (CR). Although not formally tested, survival outcomes appeared similar with pembrolizumab monotherapy versus chemotherapy (hazard ratio [HR] 0.92; 95% CI, 0.77-1.11). This post hoc exploratory analysis examined efficacy outcomes in patients with complete response (CR) to pembrolizumab or chemotherapy in KEYNOTE-361.
As a reminder, in the study patients with advanced UC were randomly assigned 1:1:1 to receive first-line pembrolizumab (200 mg IV every 3 weeks for up to 2 years) ± chemotherapy (1000 mg/m2 gemcitabine on day 1 and day 8 + cisplatin [70 mg/m2] or carboplatin [area under the concentration curve of 5 mg/ml/min] on day 1 of each 3-week cycle) or chemotherapy alone. Patients were stratified by PD-L1 combined positive score (≥10 vs <10) and investigator’s choice of platinum (cisplatin vs carboplatin).
For this specific post hoc exploratory analysis, the endpoints were duration of response (DOR) and progression-free survival (PFS) by RECIST v1.1 by blinded independent central review and overall survival (OS) in patients who achieved a CR in the pembrolizumab monotherapy or chemotherapy arms.
Functionally, though not explicitly stated, this compares Pembro monotherapy versus chemotherapy in the first line setting.
The flow of patients is summarized below:
Overall, 34 of 307 patients (11.1%) in the pembrolizumab arm and 43 of 352 patients (12.2%) in the chemotherapy arm had a CR.
Demographics of this cohort is seen below:
On quick review of the above, patients seemed similar except for sites of metastatic disease – pembo monotherapy patients had more visceral mets while chemotherapy patients had more nodal mets.
Median follow-up (time from randomization to the data cutoff date) for patients with CR was 30.7 months (range, 22.6-42.3). Median DOR was not reached (NR; range, 4.4+ to 36.1+ months) in the pembrolizumab arm and 12.8 months (range, 2.1+ to 36.3+) in the chemotherapy arm; 75.5% and 37.1% of patients, respectively, remained in CR for ≥24 months.
Median PFS was NR (95% CI, 30.3-NR) with pembrolizumab and 15.1 months (95% CI, 8.8-NR) with chemotherapy (HR, 0.32 [95% CI, 0.15-0.70]). The estimated 24-month PFS rates were 75.5% and 42.2% in the pembrolizumab and chemotherapy arms, respectively.
Median OS was NR (95% CI, NR-NR) with pembrolizumab and NR (95% CI, 25.1-NR) with chemotherapy (HR, 0.20 [95% CI, 0.06-0.70]). The estimated 24-month OS rates were 94.1% and 69.5% in the pembrolizumab and chemotherapy arms, respectively.
Overall, 9 patients (26.5%) in the pembrolizumab arm and 21 patients (48.8%) in the chemotherapy arm experienced disease progression after an initial CR. Among patients who achieved CR, 2 patients (5.9%) in the pembrolizumab arm and 22 patients (51.2%) in the chemotherapy arm received subsequent therapy.
I think this is a very interesting analysis. While the CR rates for pembro monotherapy versus chemotherapy were similar in the first line setting, the long term outcomes appear to be very different. Patients who are treated with Pembro monotherapy had a much longer PFS and OS, and a more durable response.
Unfortunately there did not appear to be any significant markers that could serve as selection criteria for choice of therapy. as the authors note, further investigation into patient selection is needed to determine which patients could benefit most from first-line pembrolizumab.
Presented by: Ozgur Ozyilkan, Prof. MD, Adana Baskent Üniversitesi, Adana, Turkey
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis, @tchandra_uromd @UCDavisUrology on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
References: