Dr. Antonia And Colleagues Report On The Combination Of Durvalumab And Tremelimumab

Optimal management of NSCLC now requires that tumours be screened for a certain range of predictive and prognostic biomarkers that help to predict sensitivity to targeted therapy and estimate prognosis respectively . For NSCLC, much of the work in the past years has been focussed on mutations of the epidermal growth factor receptor (EGFR) and on the abnormal fusion of the anaplastic lymphoma kinase (ALK) being inhibited successfully with EGFR tyrosine kinase inhibitors (TKI) and crizotinib respectively. Targeted agents are now being rationally designed to inhibit particular mutations leading to a more streamlined clinical trial process. In this review, we will examine the major subtypes of driver mutations that have been identified in NSCLC and relevant targeted therapies available both now, and in the foreseeable future.

A key factor in the development of tumors is the ability of cancerous cells to evade recognition from the bodies’ natural defense against cancer, the immune system. Immunotherapies effectively block the pathways that shield cancerous cells from being identified, and thus the promote the bodies own anti-tumor response. However, one challenge to immunotherapy has been its combination with chemotherapy, the mainstay of cancer treatment. While chemotherapy is extremely effective in stopping the rapid division of cancerous cells, its toxic immunosuppressive side-effect make it difficult to combine with

2. Denosumab has been FDA approved for 2 indications rather than 1 which is true for most of its competition. Both the conditions are prevalent in the population and their incidence is growing. This will allow the drug to tap unmet needs for the available market.

Some of traditional drugs may be effective in patients whose cancers have a specific molecular target, and not for other patients. To solve this problem of patient-specificity, pharmaceutical research have seen the expansion of individually tailored cancer treatment, which is an application of targeted therapy, and this is where biopharmaceuticals are. As an increasing part of the population is diagnosed with cancer and as these patients live longer, increasing care will be given to patients who have received these drugs. Moreover, in the case of cancer therapy, those drugs and especially with mABs are a promise of less side effects : recombinant DNA technology makes it possible to genetically engineer an antibody to reduce the risk of host immune response.

Like most diseases there are treatments and drugs used to treat the cancer. These treatments include chemotherapy, radiation, surgery, medicinal therapy used to target specific cells, and biological therapy used to help strengthen the immune system. Medicine that is used during the stages of melanoma are “Vemurafenib (Zelboraf), dabrafenib (Tafinlar) and trametinib (Mekinist) are targeted therapy drugs used to treat advanced melanoma.” (Mayo Clinic Staff 2016). More test such as biopsies are taken after targeted therapy to analyze how well the drugs are helping diminish the cancerous

For many types of cancers, we have been using the same base drug (first line treatment) for ten years or even longer. As companies find new drugs to fight the cancers, they hope that it will be the miracle drug that will eradicate the cancer, but it usually isn’t. When they reach this conclusion, instead of returning to the chalkboard and continuing to work to improve the drug, they put the drug on the market as is, and hope it will achieve something. Not only are they putting these drugs on the market but they put price tags on them that would bankrupt anyone without some sort of third party payer. The combination of all of these drugs make up what doctors

WEDNESDAY, March 4, 2015 (HealthDay News) -- U.S. Food and Drug Administration approval of Opdivo (nivolumab) has been expanded to include advanced non-small cell lung cancer (NSCLC), the agency said Wednesday in a news release.

Vogel, Charles L., et al. "Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer." Journal of Clinical Oncology 20.3 (2002): 719-726.

Several ongoing trials are addressing the intensification of adjuvant chemotherapy in TNBC patients, either through integration of novel agents into the adjuvant setting such as platinum, X, ixabepilone, or bevacizumab, or through introduction of maintenance therapy such as X (CIBOMA and SYSUCC-001) or bevacizumab (BEATRICE). Preliminary results of the CREATE-X (JBCRG-04) trial by the Japan Breast Cancer Research Group were presented at the 2015 San Antonio Breast Cancer Symposium (Toi, , et al.2016). The trial randomized 910 patients to observation versus 8 cycles of X therapy, and reported improved rates of 2-year DFS (87.3 vs. 80.5%; p = 0.001) and OS (96.2 vs. 93.9%; p = 0.086) with X. All of the observed benefit was driven by the improved outcome in the ER-

Despite current advances in both biological understanding of the disease and clinical management through systemic chemotherapy, improvements in survival rates continue to remain scarce, with only 3% of patients surviving over 5 years (Singh et al., 2015). At the point of diagnosis, only 20% of patients display localised disease and hence susceptibility to surgical resection and successful chemotherapeutic intervention (Indolfi et al., 2016). Therefore, for the majority of PDAC patients, tumours remain asymptomatic until an advanced-disease stage upon metastasis to the liver and other organs (Singh et al., 2015). The delayed manifestation of overt clinical symptoms, such as jaundice, pain and weight loss severely constrict treatment

As the world continues to suffer from these devastating diseases, researchers continue to find alternative therapeutic ways of addressing cancer treatment. It is on this premise that various immunotherapeutic alternatives have emerged and currently garnering the greatest level of attention and already raising hope throughout the world in addressing the treatment of NSCLC. However, this can no longer be viewed as a discovery but a wave in the medicine world that began in the 20th century. Various researchers have found the importance of the role of immune systems in fighting the growth of tumor caused by cancer cells. A study by Huncharek (2000) stated that specific immune boosters are capable of eliminating preclinical cancers. In contrast, Jermal et al. (2011) found that immunotherapy is an effective approach for the treatment of tumors that have already turned into solid. Similarly, the researchers highlighted that immunotherapy can be an effective approach to the treatment of melanoma as well as renal cell cancers (Lasalvia-Prisco, 2008). However, Jemal et al. (2011) noted that immunotherapy cannot achieve much in cancer treatment due to limitation brought about by the emission of immunosuppressive cytokines and subsequent loss of antigen expressions. Recent development in research studies on the immunotherapy approach to cancer treatment continues to elicit mixed reactions among researchers of medicinal ecology (Jadad et al., 1996). However, recent development in

2 small, single arm trials in 3rd line after platinum based and docetaxel chemo failure with unprecedented objective response rates, together with 2 1st line randomized trials adding gefitinib to chemo in first line and showing no benefit, were reviewed.

Cancer is the uncontrollable division and growth of abnormal cells resulting in formation of an aggressive tumour. In some forms of Breast cancer, the cells proliferate uncontrollably due to over-expression of the protein HER2 (Human Epidermal Growth Factor Receptor 2); a receptor embedded within the membrane of cells, allowing for the transfer of signals outside to inside the cell. Trastuzumab is a monoclonal antibody administered through intravenous infusion, to be taken on its own or in combination with one or more chemotherapy regimens. It reduces risk of the cancer reoccurring or spreading by inhibiting the effects of HER2, and enhancing the body’s immune system.

Afterward in 2015, FDA approved alectinib in the USA, for crizotinib-resistant patients with ALK-positive NSCLC and this year (2017) alectinib receives EU approval for patients with previously treated ALK-positive NSCLC. Starting from the AF-001JP trial, phase I part selected as recommended a dose of 300 mg BID and the phase II arm reported an ORR of 93.5% in 46 patients treated at 300 mg BID [47]. However, a second phase I/II study (NCT01588028) in crizotinib pre-treated Western patients with ALK (+) NSCLC increased the MTD to 600 mg BID and subsequent results from the phase II part of study reported ORR in 55% of 44 patients and intracranial responses in 52% of the 21 patients with measurable CNS metastases [45]. This dose has been further evaluated in two single-arm phase II trials, one including 87 patients from North America (NCT01871805) [48], and the other 138 patients from 16 different countries (NCT01801111) [46] whose disease progressed on crizotinib. Treatment with alectinib resulted in ORRs of 47.8% and 49.2%; median PFS was 6.3 and 8.9 months; duration of response continued for a median of 7.5 and 11.2 months, and intracranial response for patients with baseline CNS disease were

Unlike Gilead that has only one product in its Oncology line, Bristol-Myers Squibb presently have four different drugs namely: Erbitux –an epidermal growth factor receptor (EGFR) antagonist for the treatment of Head & Neck cancer and Colorectal cancer,(2) Opdivo (nivolumab) for the treatment of unresectable or metastic melanoma and lungs cancer, (3) Syrcel( dasatinb) for the treatment of newly diagnosed adult with Philadelphia chromosome –positive (ph+) chronic myeloid leukemia and (4) Yervoy (ipilimumob) for the treatment of melanoma a type of skin cancer that spread and as such cannot be remove by surgery. Like Seattle Genetics, the company products use either Antibody-drug Conjugate (ADC) though in a different version by linking potent cytotoxic to monoclonal antibodies targeted to specific tumor cells or immune-oncology, an innovative technology that unlocks the body own immune system to fight against cancerous cells. It also expanded its focus to Nolch inhibitor (used in blocking powerful pathway that promotes tumor cell survival for certain other types of cancer. (Bristol-Myer Squibb, 2014) Because the technology is similar but used differently, BMS would be considered a close competitor who currently has the advantage of having four targeted specific drugs and 12 other oncology and immune-oncology in various trial phases.