Phase 2 study of pembrolizumab in patients with advanced rare cancers. Issue 1 (17th March 2020)

• Record Type: Journal Article
• Authors: Naing, Aung; Meric-Bernstam, Funda; Stephen, Bettzy; Karp, Daniel D; Hajjar, Joud; Rodon Ahnert, Jordi; Piha-Paul, Sarina A; Colen, Rivka R; Jimenez, Camilo; Raghav, Kanwal P; Ferrarotto, Renata; Tu, Shi-Ming; Campbell, Matthew; Wang, Linghua; Sabir, Sarjeel H; Tapia, Coya; Bernatchez, Chantale; Frumovitz, Michael; Tannir, Nizar; Ravi, Vinod; Khan, Saria; Painter, Jeane M; Abonofal, Abulrahman; Gong, Jing; Alshawa, Anas; McQuinn, Lacey M; Xu, Mingxuan; Ahmed, Sara; Subbiah, Vivek; Hong, David S; Pant, Shubham; Yap, Timothy A; Tsimberidou, Apostolia M; Dumbrava, Ecaterina E Ileana; Janku, Filip; Fu, Siqing; Simon, Richard M; Hess, Kenneth R; Varadhachary, Gauri R; Amir Habra, Mouhammed;
• Is Part Of: Journal for immunotherapy of cancer. Volume 8:Issue 1(2020)
• Publication Date: 2020-03-17
• Subjects: oncology -- tumours; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2019-000347
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : 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