#Keynote 048 trial#
#Keynote 048 plus#

Thus, the real-world benefits of pembrolizumab plus chemotherapy (pembrolizumab regimen) in Japanese patients with R/M SCCHN remain unclear.

#Keynote 048 trial#

In addition, the results of the subgroup analysis of the Checkmate 141 trial for the Asian population also suggest that the effects of checkpoint inhibitors may differ substantially between races ( 11).

However, patient populations that are not included in clinical trials need to be treated in real-world settings thus, there is a data gap between clinical trials and real-world settings. Based on these results, the approval of these two anti-PD-1 monoclonal antibodies in Japan has led to the current use of nivolumab in patients with platinum-refractory R/M SCCHN and pembrolizumab (plus chemotherapy) as the standard first-line treatment for R/M SCCHN. Furthermore, the KEYNOTE-048 trial showed that pembrolozumab, another anti-PD-1 monoclonal antibody, as monotherapy or in combination with chemotherapy (platinum plus 5-fluorouracil), improved OS compared to the EXTREME regimen, especially in R/M SCCHN patients with PD-L1 expressing tumors ( 10). In fact, the Checkmate141 trial showed that nivolumab, an anti-PD-1 monoclonal antibody, significantly prolonged OS compared to the investigator’s choice monotherapy in platinum-refractory R/M SCCHN, a population with a poor prognosis for which no previous randomized controlled trial has previously reported any survival benefit ( 9).

Virus-associated SCCHN such as nasopharyngeal and oropharyngeal SCC evade tumor T-cell immunity due to persistent viral infection thus, ICIs are expected to be effective for patients with R/M SCCHN ( 6). Furthermore, a high tumor mutation burden is frequently observed in SCCHN as in malignant melanoma ( 7) and lung cancer ( 8). SCCHN is a malignancy in which the immune surveillance mechanism is suppressed due to the decreased function of tumor-infiltrating lymphocytes (TIL), increased function of regulatory T-cells (T-reg), and overexpression of cancer antigens ( 6). ICIs have demonstrated durable improvements in patient outcomes by regulating immune escape through the blockade of programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and programmed cell death ligand 1/2 (PD-L1/2), the ligands for PD-1 ( 4, 5). Recently, immune checkpoint inhibitors (ICIs) have been developed and used to treat various types of malignancies, including R/M SCCHN, resulting in a paradigm shift in the management of patients with R/M SCCHN. However, the prognosis of R/M SCCHN did not improve dramatically until the advent of immunotherapy, with a median overall survival (OS) of less than 1 year. in 2008, the Extreme regimen was widely used until very recently as the standard first-line treatment for patients with recurrent/metastatic SCCHN (R/M SCCHN), which is a combination of cisplatin (CDDP)/carboplatin (CBDCA) plus 5-fluorouracil and cetuximab, showing better treatment outcomes than platinum-based chemotherapy plus 5-fluorouracil ( 3). Based on the results of the EXTREME trial reported by Vermorken et al. More than half of the patients with advanced SCCHN develop locoregional or distant recurrence within 3 years thus, their prognosis is poor ( 1, 2). Squamous cell carcinoma of the head and neck (SCCHN) accounts for the majority of malignant tumors of the head and neck and is often observed as a locally advanced disease. Recurrent/metastatic squamous cell carcinoma.Conclusion: The observed therapeutic efficacy and safety of pembrolizumab in real-world clinical practice was consistent with the data of the KEYNOTE-048 trial. Immune-related adverse events (irAEs) occurred in 16 out of 32 patients (50.0%) during treatment however, there were no irAEs greater than grade 4. The Kaplan–Meier analysis showed that patients with favorable objective responses and an Eastern Cooperative Oncology Group performance status of 0 had longer survival. Fourteen patients received pembrolizumab alone, whereas the others received pembrolizumab with chemotherapy. Results: The median follow-up duration was 9.8 months (range=1.6-25.1 months). The primary endpoint of the study was overall survival. Patients and Methods: Thirty-two Japanese patients with R/M SCCHN treated with the pembrolizumab regimen between January 2020 and January 2022 were analyzed. Background/Aim: This Japanese single-center retrospective cohort study aimed to evaluate the real-world therapeutic outcomes of pembrolizumab or pembrolizumab plus chemotherapy (pembrolizumab regimen) as first-line therapy for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).