Aung Naing, MD, FACP of MD Anderson discusses the Phase 2 study of pembrolizumab in patients with advanced rare cancers.
There is a poor prognosis for patients with advanced rare cancers with few treatment options. We aimed to test pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced, rare cancers as immunotherapy is successful across multiple types of cancer.
In this open-label, phase 2 study, nine tumor-specific cohorts and a 10th cohort for other unusual histologies were included in patients with advanced rare cancers whose tumors had progressed to standard therapies, if appropriate, during the previous 6 months. Pembrolizumab 200 mg was administered every 21 days on an intravenous basis. The key endpoint was a 27-week non-progression rate (NPR); the secondary endpoints were protection and tolerability, objective response rate (ORR) and clinical benefit rate (CBR).
This study included a total of 127 patients treated between August 15, 2016 and July 27, 2018. The NPR at 27 weeks was 28 percent at the time of the data cut-off (95 percent CI, 19 percent to 37 percent ). In 15 of 110 (14 percent) evaluable patients, a reported objective response (OR) was seen (complete response in one and partial response in 14). 38 percent (n=42) was CBR, described as the percentage of patients with an OR or stable disease ~4 months. In 11 out of 15 patients with OR at the last follow-up, care was continuing. The NPR at 27 weeks was 36%, ORR 31% and CBR 38% in the cohort with squamous cell carcinoma (SCC) of the skin. NPR at 27 weeks was 31 percent, ORR 15 percent and CBR 54 percent in patients with adrenocortical carcinoma (ACC). In patients with unknown primary carcinoma (CUP), NPR was 33 percent, ORR 23 percent and CBR 54 percent at 27 weeks. NPR at 27 weeks was 43 percent, ORR 0 percent and CBR 75 percent in the paraganglioma-pheochromocytoma cohort. In 66 of the 127 (52 percent) patients, treatment-related adverse effects (TRAEs) occurred, and 12 (9 percent) had grade 3 TRAEs. Fatigue (n=25) and rash (n=17) were the most common TRAEs. Six deaths occurred, all of which were unrelated to the study drug.
Further evaluation of pembrolizumab in this patient population confirms the favorable toxicity profile and antitumor activity seen in patients with skin, ACC, CUP, and paraganglioma-pheochromocytoma SCCs.
NCT02721732 Trial registration number