TY - JOUR
T1 - Phase 2 study of pembrolizumab in patients with advanced rare cancers
AU - Naing, Aung
AU - Meric-Bernstam, Funda
AU - Stephen, Bettzy
AU - Karp, Daniel D.
AU - Hajjar, Joud
AU - Rodon Ahnert, Jordi
AU - Piha-Paul, Sarina A.
AU - Colen, Rivka R.
AU - Jimenez, Camilo
AU - Raghav, Kanwal P.
AU - Ferrarotto, Renata
AU - Tu, Shi Ming
AU - Campbell, Matthew
AU - Wang, Linghua
AU - Sabir, Sarjeel H.
AU - Tapia, Coya
AU - Bernatchez, Chantale
AU - Frumovitz, Michael
AU - Tannir, Nizar
AU - Ravi, Vinod
AU - Khan, Saria
AU - Painter, Jeane M.
AU - Abonofal, Abulrahman
AU - Gong, Jing
AU - Alshawa, Anas
AU - McQuinn, Lacey M.
AU - Xu, Mingxuan
AU - Ahmed, Sara
AU - Subbiah, Vivek
AU - Hong, David S.
AU - Pant, Shubham
AU - Yap, Timothy A.
AU - Tsimberidou, Apostolia M.
AU - Dumbrava, Ecaterina E.Ileana
AU - Janku, Filip
AU - Fu, Siqing
AU - Simon, Richard M.
AU - Hess, Kenneth R.
AU - Varadhachary, Gauri R.
AU - Amir Habra, Mouhammed
PY - 2020/3/1
Y1 - 2020/3/1
N2 - BACKGROUND: Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers. METHODS: In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR). RESULTS: A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma-pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug. CONCLUSIONS: The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma-pheochromocytoma supports further evaluation of pembrolizumab in this patient population. TRIAL REGISTRATION NUMBER: NCT02721732.
AB - BACKGROUND: Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers. METHODS: In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR). RESULTS: A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma-pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug. CONCLUSIONS: The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma-pheochromocytoma supports further evaluation of pembrolizumab in this patient population. TRIAL REGISTRATION NUMBER: NCT02721732.
KW - oncology
KW - tumours
UR - http://www.scopus.com/inward/record.url?scp=85081994525&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081994525&partnerID=8YFLogxK
U2 - 10.1136/jitc-2019-000347
DO - 10.1136/jitc-2019-000347
M3 - Article
C2 - 32188704
SN - 2051-1426
VL - 8
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 1
ER -