Pembrolizumab in Asia‐Pacific patients with advanced head and neck squamous cell carcinoma: Analyses from KEYNOTE‐012

Abstract

KEYNOTE‐012 was a phase Ib, multicohort study designed to investigate efficacy and safety of pembrolizumab in advanced solid tumors. Results from the subset of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) from the Asia‐Pacific region are reported. Patients with recurrent/metastatic HNSCC, measurable disease (RECIST version 1.1), and ECOG performance status (PS) 0‐1 were eligible for enrollment in the HNSCC expansion cohort. Patients received pembrolizumab 200 mg every 3 weeks. Response was assessed every 8 weeks. Co‐primary end‐points were safety and overall response rate (RECIST version 1.1, central review). Secondary end‐points included overall survival and response duration. Patients enrolled at any of the five centers throughout the Asia‐Pacific region were included in these analyses. Twenty‐six patients with HNSCC from the Asia‐Pacific region received pembrolizumab. The median age was 62 years, 65% of patients had ECOG PS 1, and 62% had received two or more prior therapies for recurrent/metastatic disease. Sixteen (62%) patients experienced a treatment‐related adverse event of any grade, including two (8%) patients who experienced one or more events of grade 3 severity. No treatment‐related deaths occurred. The overall response rate was 19% (95% confidence interval, 7%‐39%). After a median follow‐up of 12 months (range, 2‐21 months), a median response duration was not reached (range, 6 to 17+ months); four of five responses lasted ≥6 months. Median overall survival was 11.6 months (95% confidence interval, 4.7‐17.7 months). Pembrolizumab was well tolerated and had durable antitumor activity in patients with HNSCC from the Asia‐Pacific region. (Trial registration no. NCT01848834.)

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

“…To determine PD‐L1 immunopositivity, the recommended cut‐off values are summarised in Table . These thresholds were established according to clinical response to the associated immune check‐point inhibitor in various clinical trials for UC,, HSCC and BC …”

Management of Adverse Events in Cancer Patients Treated With PD-1/PD-L1 Blockade: Focus on Asian Populations

“…This is confirmed by the endocrinopathy profile in Asian populations. As observed in early-phase trials in Japan (Hamanishi et al, 2015; Yamazaki et al, 2017), China (Huang et al, 2018), and Asia-Pacific regions (Tahara et al, 2018), hypothyroidism was one of the top 3 most common AEs with anti-PD-1/PD-L1 therapies. In a real-world retrospective study of monotherapy with nivolumab or pembrolizumab in patients with NSCLC in Taiwan, abnormal thyroid function was the most common adverse effect (5/74, 6.5%).…”

“…Therefore, the information of PD-1/PD-L1 blockade in Asians is far from systematic or comprehensive. By now, the results of trials on nivolumab (Hamanishi et al, 2015; Kang et al, 2017; Kudo et al, 2017; Maruyama et al, 2017; Nishio et al, 2017; Yamazaki et al, 2017), camrelizumab (Fang et al, 2018; Huang et al, 2018, Huang et al, 2019; Mo et al, 2018), pembrolizumab (Shimizu et al, 2016; Tahara et al, 2018; Nishio et al, 2019), avelumab (Doi et al, 2018), and atezolizumab (Mizugaki et al, 2016) in Asian populations have been published ( Table 1 ). Here, the most common treatment-related AEs (TRAEs) of any grade and TRAEs of grades 3–5 reported in the above articles were summarized per organ system ( Figure 2 ).…”

“…One patient with advanced NSCLC developed grade 3 ALT elevation, grade 3 AST elevation, and grade 1 pneumonitis simultaneously on day 42 and further developed grade 3 hyponatremia after termination of pembrolizumab (Shimizu et al, 2016). In a phase 1b study (KEYNOTE-012) in Asia-Pacific patients with advanced head and neck squamous cell carcinoma, two (8%) patients experienced serious TRAEs, one of which was a grade 2 ILD that resulted in drug discontinuation (Tahara et al, 2018).…”

Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma

“…PD-L1's immune checkpoint response has been extensively studied and plays predominant roles in immune surveillance during tumor development and immune escape of cancer cells [41]. Immune checkpoint inhibitors, including nivolumab and pembrolizumab, have been approved to treat OSCC [42][43][44][45][46]. Despite the importance of the immune checkpoint, the clinicopathological effects of PD-L1 expression in patients with OSCC remain unclear.…”