Immune checkpoint therapy that targets the programmed cell death protein 1 (PD-1) may provide clinical benefit for these patients. (27.3%) had stable disease, corresponding to a disease control rate of 59.1%. Four patients had confirmed disease progression, 2 of whom had continuous PROTAC FAK degrader 1 progression over the target lesion after shrinkage of other metastases. One patient developed immune-related pneumonitis that resolved quickly after steroid treatment. Another patient developed itchy skin rashes immediately after administration of pembrolizumab, and this was controlled by an antihistamine. There were no other severe adverse effects. Pembrolizumab is beneficial and well-tolerated for some patients with refractory R/M HNSCC. However, it is important to identify biomarkers to identify the most responsive patients PROTAC FAK degrader 1 when designing future trials. value .05 was defined as significant. 3.?Results 3.1. Patient characteristics Between January 2016 and December 2016, we recognized 22 individuals (5 ladies and 17 males) with R/M HNSCC who received immunotherapy with pembrolizumab (Table ?(Table1).1). The median age was 61 years (interquartile range [IQR]: 47C69 years). The primary sites of the HNSCC were the oral cavity (n?=?9, 40.9%), oropharynx (n?=?2, 9.1%), hypopharynx (n?=?4, 18.2%), neck lymphadenopathy with unknown main site (n?=?4, 18.2%), while others (nasopharyngeal malignancy [n?=?2, 9.1%] and squamous cell carcinoma transformed from thyroid malignancy [n?=?1, 4.5%]). Three individuals received combined local palliative radiation over the primary sites of recurrent tumors. No additional chemotherapy or targeted medicines were given with pembrolizumab. Table 1 Baseline characteristics of individuals with R/M HNSCC who received pembrolizumab and whose malignancy was or was not controlled (n?=?22). Open in a separate windowpane We also evaluated the front-line treatments that individuals received after initial confirmation of R/M HNSCC. Five individuals (22.7%) received pembrolizumab like a first-line treatment PROTAC FAK degrader 1 after confirmation of R/M HNSCC due to poor performance status and general health status, early relapse in the 6 months after a previous cisplatin/5-FU treatment, or the patient’s request to avoid chemotherapy. Nine (40.9%) individuals received a first-line systemic therapy before pembrolizumab, and 8 (36.4%) received 2 or more systemic treatments before pembrolizumab. The systemic chemotherapy regimens given Rabbit Polyclonal to GRAP2 prior to pembrolizumab were cisplatin or carboplatin combined with 5-FU (n?=?9, 40.9%), a methotrexate-based routine (n?=?3, 13.6%), cetuximab-based chemotherapy (n?=?7, 31.8%), while others (n?=?9, 40.9%). Human being papillomavirus (HPV) status was retrospectively evaluated within these individuals. Only 4 individuals experienced p16 staining data, including 3 individuals (1 oropharyngeal SCC, 1 nasopharyngeal SCC, and 1 hypopharyngeal SCC) with p16 bad and 1 patient (Patient No. 9, oropharyngeal SCC) with p16 positive. HPV polymerase chain reaction (PCR) exam for tumor cells HPV had shown undetectable HPV DNA in the patient with p16 staining positive. The correlation of HPV status with response rate cannot be assessed due to small number. 3.2. End result There were 17 evaluable individuals (77.3%) who received at least 1 image follow-up after pembrolizumab treatment. The median PFS was 140 days, and the OS was 169 days (Fig. ?(Fig.1).1). Based on RECIST criteria (ver. 1.1), 2 individuals (9.1%) had a complete response (CR), 5 individuals (22.7%) had a partial response (PR), and 6 individuals (27.3%) had stable disease, corresponding to a disease control rate (DCR) of 59.1%. Six individuals who ever showed controlled disease under front-line systemic treatment are all responsive to pembrolizumab treatment (100%). Among the additional 11 individuals who failed to response to front-line systemic treatment, 6 (63%) showed controlled disease after pembrolizumab salvage treatment. Number ?Figure22 shows a waterfall storyline of tumor size and a swimmer storyline of treatment period for each of the 17 evaluable individuals. We describe 4 notable individuals below, 2 with total remission, 1 with nonconcordant changes of metastatic lesions and target lesions, and another with immune-related pneumonitis. Open in a separate window Number 1 KaplanCMeier survival curves for (A).