Avelumab, an anti-PD-L1 monoclonal antibody, shows activity in various tumour types

Abstract

During the past 5 years, immune checkpoint inhibitors have revolutionised the management and treatment of cancer, because they have been associated with striking improvements in clinical outcomes in patients with some tumour types. For example, the use of checkpoint inhibitors has changed the natural history of melanoma with a pronounced increase in patients' survival. 1 Robert C Long GV Brady B et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015; 372: 320-330 Crossref PubMed Scopus (4060) Google Scholar , 2 Ribas A Puzanov I Dummer R et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015; 16: 908-918 Summary Full Text Full Text PDF PubMed Scopus (1230) Google Scholar These agents have also been tested in many other tumour types, such as renal cancer, urothelial cancer, and squamous cell cancer of the head and neck, with promising results and have subsequently gained approval from the regulatory authorities. In non-small-cell lung cancer (NSCLC), survival rates have improved in recent years, both as a result of advances in disease management—including the addition of new-generation agents to the therapeutic armamentarium—and supportive care. Indeed, the development of many active and better-tolerated drugs, such as bevacizumab, pemetrexed, nab-paclitaxel, and, more recently, nintedanib and ramucirumab, has increased the number of available treatment options for patients with NSCLC. Two anti-PD-1 monoclonal antibodies, nivolumab and pembrolizumab, have already been approved for the treatment of NSCLC in the second-line setting or beyond, 3 Borghaei H Paz-Ares L Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015; 373: 1627-1639 Crossref PubMed Scopus (6826) Google Scholar , 4 Brahmer J Reckamp KL Baas P et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015; 373: 123-135 Crossref PubMed Scopus (6294) Google Scholar , 5 Herbst RS Baas P Kim DW et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016; 387: 1540-1550 Summary Full Text Full Text PDF PubMed Scopus (4591) Google Scholar as has the anti-PD-L1 antibody atezolizumab. 6 Rittmeyer A Barlesi F Waterkamp D et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017; 389: 255-265 Summary Full Text Full Text PDF PubMed Scopus (3203) Google Scholar Additionally, on Oct 24, 2016, pemrbolizumab also gained approval for the first-line treatment of NSCLC in a small subgroup of patients with high expression (>50%) of PD-L1. 7 Reck M Rodriguez-Abreu D Robinson AG et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016; 375: 1823-1833 Crossref PubMed Scopus (6306) Google Scholar Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trialAvelumab has an acceptable toxicity profile up to 20 mg/kg and the maximum tolerated dose was not reached. Based on pharmacokinetics, target occupancy, and immunological analysis, we chose 10 mg/kg every 2 weeks as the dose for further development and phase 3 trials are ongoing. Full-Text PDF Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trialAvelumab showed an acceptable safety profile and antitumour activity in patients with progressive or treatment-resistant NSCLC, providing a rationale for further studies of avelumab in this disease setting. Full-Text PDF Correction to Lancet Oncol 2017; 18: 556–57Kotsakis A, Georgoulias V. Avelumab, an anti-PD-L1 monoclonal antibody, shows activity in various tumour types. Lancet Oncol 2017; 18: 556–57—In this Comment, the term ‘immune-related’ should have read ‘infusion-related’ in two phrases. The two affected sentences should have read as follows: “However, an important finding from these two studies was that the frequency of infusion-related reactions exceeded 20%; infusion-related reactions are uncommon with the other approved immunotherapeutic agents, with an estimated frequency of about 1–2%” and “Once again, ongoing phase 3 trials ( NCT02395172 , NCT02576574 ) might shed light on the frequency, significance, and severity of infusion-related adverse events and how best to manage them.” These corrections have been made to the online version as of July 26, 2017. Full-Text PDF