Non-small cell lung cancer (NSCLC) is a leading cause of\u00a0death among cancer patients. The 5-year overall survival rate\u00a0in patients with localized cancer is 55.2 %, and this decreases\u00a0to 4.3 % in those with advanced disease. Since the development of platinum-based therapy two decades ago, there has\u00a0been little progress in the treatment of advanced stage\u00a0NSCLC. Agents like EGFR and ALK inhibitors showed efficacy in the first line treatment of NSCLC; however, their role\u00a0is limited to a subset of patients who carry sensitizing mutations which are almost exclusively found in tumors with adenocarcinoma histology. No significant progress has been\u00a0made in the second line treatment of NSCLC since the approval of docetaxel in 1999. This remained the standard agent in\u00a0this setting until recently. The advent of checkpoint\u00a0inhibitors in the treatment of non-small lung cancer, particularly the anti-PD-1 monoclonal antibodies nivolumab and\u00a0pembrolizumab, has brought new hope to many patients with\u00a0advanced stage disease who failed first line treatment with platinum-based, doublet chemotherapy.<\/p>\n
Nivolumab<\/a> was compared to docetaxel in two pivotal studies: checkmate 017 (nivolumab vs docetaxel in advanced\u00a0stage squamous cell lung cancer) and checkmate 057 (nivolumab vs docetaxel in advanced stage non-squamous cell\u00a0lung cancer). In both studies, nivolumab performed superiorly\u00a0to docetaxel demonstrating higher efficacy, improved survival\u00a0benefit, and a better safety profile. In checkmate 017, the hazard ratio (HR) for overall survival (OS) in patients receiving\u00a0nivolumab compared to those who were allocated to docetaxel\u00a0was 0.52 (95 % CI, 0.35\u20130.75) in 152 patients <65 years, 0.56\u00a0(95 % CI, 0.34\u20130.91) in 91 patients aged 65 to 75 years, and\u00a01.85 (95 % CI, 0.76\u20134.51) in 29 patients aged \u226575 years.<\/p>\n Pembrolizumab<\/a> garnered accelerated approval in NSCLC\u00a0based on its performance in the phase 1b Keynote-001 study. Subsequent to this pivotal study, Keynote-010 compared\u00a0pembrolizumab to docetaxel in a three-arm, phase 2\/3 randomized trial. Patients were divided into three groups:\u00a0345 received pembrolizumab 2 mg\/kg, 346 received\u00a0pembrolizumab 10 mg\/kg, and 343 received docetaxel.\u00a0Pembrolizumab, at both doses, outperformed docetaxel across\u00a0all study populations. The HR for OS in the pembrolizumab\u00a02 mg\/kg group was 0.71 (95 % CI, 0.58\u20130.88) compared to\u00a0docetaxel. The median OS of this dose was 10.4 months.\u00a0Pembrolizumab 10 mg\/kg had a HR of 0.61 (0.49\u20130.75)\u00a0and median OS of 12.7 months, and docetaxel had a median OS of 8.5 months. The benefit was more significant in\u00a0patients with PD-L1<\/a> expression higher than 50 % in their\u00a0tumor tissue. AE rates associated with pembrolizumab 2\u00a0and 10 mg\/kg were 63 and 66 %, respectively, compared\u00a0to 81 % with docetaxel. Pembrolizumab, at both doses, was\u00a0associated with a range of autoimmune events, most frequent being hypothyroidism (8 %), pneumonitis (4\u20135 %),\u00a0and hyperthyroidism (4\u20136 %).<\/p>\n Non-small lung cancer is predominantly found in older\u00a0adults. More than 50 % of patients with this diagnosis are over\u00a065 years old, and highest mortality rates are also seen in this\u00a0age group. However, most evidence used in management\u00a0of older patients with NSCLC is extrapolated from literature\u00a0on younger adults due to underrepresentation of this age category in clinical trials. The patient population included in\u00a0the aforementioned trials had a higher percentage of older\u00a0adults (approximately 40 %) compared to what is usually seen\u00a0in the literature. However, the numbers are still not representative of the actual NSCLC population. This observation is\u00a0important because while many older patients with advanced\u00a0NSCLC are already being treated with checkpoint inhibitors,\u00a0data from the main trials are not completely supportive.\u00a0Interestingly, patients aged \u226575 years had a non-significant\u00a0HR for survival of 1.85 (95 % CI, 0.76\u20130.451) in checkmate\u00a0017, and 0.90 (95 % CI, 0.43\u20131.87) in checkmate 057. In\u00a0Keynote-010, the HR for survival in patients \u226565 years was\u00a00.76 (95 % CI, 0.57\u20131.02). While these numbers might be due\u00a0to statistical reasons more than a lack of efficacy, they still put\u00a0a question mark on whether these new agents are truly effective in older patients. Aging is\u00a0associated with a decline in the\u00a0immune function which could be associated, at least hypothetically, with decreased efficacy of immune mediated\u00a0therapies. However, checkpoint inhibitors are a favorable\u00a0option in the second line treatment of older adults with\u00a0NSCLC due to their improved safety profile compared to chemotherapy. Ongoing trials are looking into combining\u00a0checkpoint inhibitors with chemotherapy or molecularly\u00a0targeted agents, use of dual checkpoint inhibition (anti-PD-1\u00a0and anti-CTLA-4), and the role of checkpoint inhibitors<\/a> in the\u00a0adjuvant setting.<\/p>\n <\/p>\n Reference:<\/p>\n Rawad Elias & Joshua Morales & Yasser Rehman & Humera Khurshid. Curr Oncol Rep (2016) 18: 47<\/p>\n Non-small cell lung cancer (NSCLC) is a leading cause of\u00a0death among cancer patients. The 5-year overall survival rate\u00a0in patients with localized cancer is 55.2 %, and this decreases\u00a0to 4.3 % […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[21],"tags":[284,129,296,277,286],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/506"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=506"}],"version-history":[{"count":1,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/506\/revisions"}],"predecessor-version":[{"id":507,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/506\/revisions\/507"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=506"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=506"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=506"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Related Products:<\/h4>\n
<\/th> <\/th> <\/th> <\/th><\/tr><\/thead> CAS Number <\/td> Product Name <\/td> Target <\/td> Description <\/td><\/tr> 1374853-91-4 <\/td> pembrolizumab<\/a><\/td> PD-1 <\/td> Pembrolizumab (formerly MK-3475 and lambrolizumab, trade name Keytruda) is a humanized antibody used in cancer immunotherapy. It targets the programmed cell death 1 (PD-1) receptor. The drug was initially used in treating metastatic melanoma. <\/td><\/tr> 946414-94-4 <\/td> nivolumab<\/a><\/td> PD-1<\/a><\/td> Nivolumab, marketed as Opdivo, is a humanized IgG4 anti-PD-1 monoclonal antibody used to treat cancer. Nivolumab works as a checkpoint inhibitor, blocking a signal that would have prevented activated T cells from attacking the cancer, thus allowing the immune system to clear the cancer. <\/td><\/tr> 477202-00-9 <\/td> Ipilimumab<\/a><\/td> CTLA4<\/a><\/td> Ipilimumab binds to CTLA4 expressed on T-cells and inhibits the CTLA4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. <\/td><\/tr><\/tbody><\/table><\/div>\n","protected":false},"excerpt":{"rendered":"