RT Journal Article
SR Electronic
T1 Phase 2 study of pembrolizumab in patients with advanced rare cancers
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000347
DO 10.1136/jitc-2019-000347
VO 8
IS 1
A1 Aung Naing
A1 Funda Meric-Bernstam
A1 Bettzy Stephen
A1 Daniel D Karp
A1 Joud Hajjar
A1 Jordi Rodon Ahnert
A1 Sarina A Piha-Paul
A1 Rivka R Colen
A1 Camilo Jimenez
A1 Kanwal P Raghav
A1 Renata Ferrarotto
A1 Shi-Ming Tu
A1 Matthew Campbell
A1 Linghua Wang
A1 Sarjeel H Sabir
A1 Coya Tapia
A1 Chantale Bernatchez
A1 Michael Frumovitz
A1 Nizar Tannir
A1 Vinod Ravi
A1 Saria Khan
A1 Jeane M Painter
A1 Abulrahman Abonofal
A1 Jing Gong
A1 Anas Alshawa
A1 Lacey M McQuinn
A1 Mingxuan Xu
A1 Sara Ahmed
A1 Vivek Subbiah
A1 David S Hong
A1 Shubham Pant
A1 Timothy A Yap
A1 Apostolia M Tsimberidou
A1 Ecaterina E Ileana Dumbrava
A1 Filip Janku
A1 Siqing Fu
A1 Richard M Simon
A1 Kenneth R Hess
A1 Gauri R Varadhachary
A1 Mouhammed Amir Habra
YR 2020
UL http://jitc.bmj.com/content/8/1/e000347.abstract
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