![\"\"](\"http:\/\/blogs.shu.edu\/cancer\/files\/2017\/06\/Fig-1-PD-L1.jpg\")
<\/a>Figure 1. PD-1 \/ PD-L1 axis. http:\/\/www.cell.com\/trends\/molecular-medicine\/references\/S1471-4914(14)00183-X<\/a><\/p><\/div>\n It received the FDA nod in May 2017 for the treatment of advanced bladder cancer<\/a>, regardless of PD-L1 status:<\/p>\n Table 1. Clinical results of durvalumab in bladder cancer. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/761069s000lbl.pdf<\/a><\/p><\/div>\n A few weeks after the approval of durvalumab for bladder cancer, excellent clinical results were announced in lung cancer<\/a> from the Phase 3 PACIFIC trial in patients with locally advanced non-small cell lung cancer (NSCLC) who had not progressed following standard platinum-based chemotherapy concurrent with radiation therapy. The study was stopped at the first planned interim analysis because patients receiving durvalumab had statistically significant increased progression-free survival (PFS). Full data, including overall survival, will be available in the future.<\/p>\n Imfinzi<\/em>\u00a0is also being tested in the 1st-line treatment of patients with NSCLC as monotherapy in the MYSTIC and PEARL Phase III trials. It is also being developed in combination with tremelimumab, a checkpoint inhibitor that targets CTLA-4, as part of the MYSTIC, NEPTUNE and POSEIDON Phase III trials.<\/em><\/p>\n There are now five approved checkpoint inhibitors<\/a> targeting the PD-1\/PD-L1 axis \u2013 Bavencio<\/a> (avelumab, PD-L1, Pfizer & Merck KGaA: Merkel Cell carcinoma) \u2013Opdivo (nivolumab<\/a>, PD-1, BMS: melanoma, squamous cell carcinoma of the head and neck \u2013 HNSCC, non-small cell lung cancer \u2013 NSCLC, bladder cancer, renal cell carcinoma, classical Hodgkin lymphoma), Keytruda (pembrolizumab<\/a>, PD-1, Merck: melanoma, NSCLC, HNSCC, classical Hodgkin Lymphoma, bladder cancer, Microsatellite Instability-High cancers), and Tecentriq (atrezolizumab<\/a>, PD-L1, Genentech: metastatic non-small cell lung cancer and bladder cancer).<\/p>\n There are now 756 clinical studies listed on clinicaltrials.gov<\/a> involving checkpoint combination trials, according to Evaluate EP<\/a>. Keytruda leads the pack, with 268<\/a> \u2014 up from 70 just 18 months ago. For Bristol-Myers it\u2019s 242, more than three times the number EP Vantage\u2019s editorial team found in 2015. The trials include PD-1\/PD-L1 checkpoints combined with other checkpoints (e.g., IDO inhibitors), cancer vaccines, antibodies to cancer-associated antigens, chemotherapy, kinase inhibitors, and many others.<\/p>\n Figure 2. Checkpoint combination trials. http:\/\/info.evaluategroup.com\/rs\/607-YGS-364\/images\/epv-pdct17.pdf<\/a><\/p><\/div>\n Given that the first checkpoint inhibitor, Yervoy (ipilimumab<\/a>, PD-1), and nivolumab and pembrolizumab are indicated for melanoma, there are many combination studies in this disease.<\/p>\n Figure 3. Checkpoint combination trials by cancer type. http:\/\/info.evaluategroup.com\/rs\/607-YGS-364\/images\/epv-pdct17.pdf<\/a><\/p><\/div>\n Because anti-CTLA4 and anti-PD-1\/PD-L1 antibodies are already on the market, and the great promise of combining these complementary approaches, checkpoint-checkpoint combinations are the most abundant. Indeed, BMS has shown that combining Yervoy and Opdivo provides for significantly enhanced effectiveness<\/a> in melanoma, but with increased toxicity \u2013 forty percent of patients cannot tolerate a full course of therapy. Studies examining how best to combine these agents to maximize effectiveness and mitigate toxicity make great sense. AstraZeneca is also pursuing the combination with durvalumab + its own CTLA-4 inhibitor in development, tremelimumab.<\/p>\n\n
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