Abstract
Outcomes by complete response to first-line pembrolizumab or platinum-based chemotherapy in advanced urothelial carcinoma (UC) in KEYNOTE-361.
Author
person
Ozgur Ozyilkan
Adana Baskent Üniversitesi, Adana, Turkey
info_outline
Ozgur Ozyilkan, Raymond S. McDermott, María José Juan-Fita, Andrey Semenov, Boris Alekseev, Raanan Berger, Woo Kyun Bae, Pongwut Danchaivijitr, Jianxin Lin, Abhishek Amar Bavle, Kentaro Imai, Cagatay Arslan
Full text
Authors
person
Ozgur Ozyilkan
Adana Baskent Üniversitesi, Adana, Turkey
info_outline
Ozgur Ozyilkan, Raymond S. McDermott, María José Juan-Fita, Andrey Semenov, Boris Alekseev, Raanan Berger, Woo Kyun Bae, Pongwut Danchaivijitr, Jianxin Lin, Abhishek Amar Bavle, Kentaro Imai, Cagatay Arslan
Organizations
Adana Baskent Üniversitesi, Adana, Turkey, Adelaide and Meath Hospital, University College Dublin, Dublin, Ireland, Instituto Valenciano de Oncología, Valencia, Spain, Ivanovo Regional Oncology Dispensary, Ivanovo, Russian Federation, P. Hertsen Moscow Oncology Research Institute, Ministry of Health of the Russian Federation, Moscow, Russian Federation, Sheba Medical Center, Ramat Gan, Israel, Chonnam National University Medical School and Hwasun Hospital, Gwangju, South Korea, Siriraj Hospital, Bangkok, Thailand, Merck & Co., Inc., Rahway, NJ, Medical Park Izmir Hastanesi, Izmir, Turkey
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Background:
In the randomized, open-label, phase 3 KEYNOTE-361 (NCT02853305) study, superior efficacy was not demonstrated with first-line pembrolizumab ± chemotherapy versus chemotherapy in patients with advanced UC. 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.
Methods:
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/m
2
gemcitabine on day 1 and day 8 + cisplatin [70 mg/m
2
] 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). End points of this post hoc exploratory analysis 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.
Results:
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. 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.
Conclusions:
This post hoc exploratory analysis suggests CRs with pembrolizumab were more durable than CRs with chemotherapy in patients with advanced UC, with corresponding longer PFS and OS. Further investigation into patient selection is needed to determine which patients could benefit most from first-line pembrolizumab. Clinical trial information: NCT02853305.
Clinical status
Clinical
1 clinical trial
11 organizations
4 drugs
6 targets
Clinical trial
A Phase III Randomized, Controlled Clinical Trial of Pembrolizumab With or Without Platinum-Based Combination Chemotherapy Versus Chemotherapy in Subjects With Advanced or Metastatic Urothelial CarcinomaStatus: Completed, Estimated PCD: 2020-04-29
Organization
Adana Baskent ÜniversitesiOrganization
Adelaide and Meath HospitalOrganization
University College DublinOrganization
Instituto Valenciano de OncologíaOrganization
Ivanovo Regional Oncology DispensaryOrganization
P. Hertsen Moscow Oncology Research InstituteOrganization
Sheba Medical Center, Or-YeudaOrganization
Siriraj HospitalOrganization
Merck & Co., Inc.Organization
Medical Park Izmir HastanesiDrug
pembrolizumabDrug
CisplatinDrug
FF-10832Drug
carboplatinTarget
PD-1Target
carboplatinTarget
cisplatinTarget
DNATarget
GemcitabineTarget
Pembrolizumab