PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population.
RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage).
CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.
AREAS COVERED: The objective of presented review is to investigate the molecular pathways of platinum medicines and HDAC inhibitors. A comprehensive literature review from 2011 to 2024 was conducted across multiple databases like MEDLINE, PubMed, Google Scholar, Science Direct, Scopus and official websites of ClinicalTrial.gov to explore publications on HDAC inhibitors, platinum drugs, and combination cancer therapies, revealing preliminary evidence of innovative treatment strategies involving HDAC inhibitors and platinum chemotherapeutics. Several new platinum (IV) complexes, with HDAC inhibitory moieties and better cytotoxicity profiles than conventional platinum drugs, are also reviewed here.
EXPERT OPINION: The above combination has great potential in cancer treatment, however managing toxicity, dosage regimens, and patient selection biomarkers are problematic. More selective HDAC inhibitors and innovative delivery techniques are potential areas for future research. An adaptation toward changing cancer therapeutic landscapes, highlights combining HDAC inhibitors with platinum-based medicines serves as a new concept for personalized medicine, however, a deeper research is still needed at this time.