Immunotherapy Bridge 2016 and Melanoma Bridge 2016: meeting abstracts

Abstract

Background: NSCLC remains a challenging disease to treat, especially because the majority of patients present with advanced disease [1]. For many of these patients the standard first-line therapy is platinumbased chemotherapy, which can prolong survival by 8-12 months in some patients and also improve disease-related symptoms [2]. The chemotherapy treatments are frequently poorly tolerated. Treatment choices following chemotherapy are limited, approved options include docetaxel, pemetrexed and erlotinib. Recent developments with immunotherapies and approval of agents such as nivolumab and pembrolizumab [3, 4] are exciting. Other immunotherapy agents such as darvolumab, atezolizumab and avelumab are also investigated and show good results. Materials and methods: Literature was reviewed about checkpoint inhibitors in metastatic NSCLC. Both the efficacy, patient reported outcomes and adverse events will be reported, with emphasis on the results from phase 3 trials. Results: Checkpoint inhibitors in development are ipilimumab and tremelimumab, they block CTLA4. Nivolumab and pembrolizumab are blocking binding of PD1 to PDL1 and PDL2. Atezolizumab and durvalumab are blocking binding of PDL1 to PD1 and CD 80. Avelumab is in early stages of research. Nivolumab trials CheckMate 017 [5] and 057 in second-line phase 3 trials and ChecMate 026 in 1st-line monotharapy vs SOC phase 3 trial were reported. In second-line nivolumab showed superiority over docetaxel in progression free survival (PFS) 3.5 vs 2.8 months, HR = 0.62, p-0.004, mOS = 9.2 vs 6 months independent to PDL1 expression in squamous histology. Adverse events were rare and manageable. Combination of nivolumab with chemotherapy and with erlotinib are being investigated. Pembrolizumab monotherapy showed responses which exceeded one year, median PFS = 6.3 months, especially high tumor proportion score (TPS) 50%, representing 23% of the screened NSCLC population. In pembrolizumab vs docetaxel, Keynote 010, median OS with pembrolizumab 2 mg/kg and at least 50% PDL1 TPS was 14.9 months vs 8.2 months on docetaxel. Adverse events were less common on pembrolizumab. PDL1 expression 50% correlated with improved RR,PFS and OS regardless of histology. Smoking status was associated with increased RR. Keynote 024 = pembrolizumab vs chemotherapy showed superiority in phase 3, chemonaive patients of pembrolizumab in OS. (=Press release only) Atezolizumab vs docetaxel, phase 2 randomized trial [6] POPLAR showed improvement in OS (HR 0.69 vs 0.73) in ITT population. Duration of response of 18.6 months compared to 7.2 months with docetaxel and well tolerated safety profile.OAK trial = phase 3 is ongoing. Durvalumab with trmelimumab phase 3 trial results are pending. Conclusion: The results of immunotherapy trials are encouraging, both from the point of improved efficacy and their tolerability. Combination treatments with immunotherapy may further improve the efficacy and prolong the lives of the patients with metastatic NSCLC. These combination treatments will replace eventually the platinum doublets in first-line treatment of metastatic NSCLC Immunotherapy in oncology: data from clinical trial K2 Immunotherapy in ovarian and endometrial cancer