Oncology Highlights - April 2017
Reading our newsletter will only take a few minutes and allows you to keep up to date with last month’s news items on oncology drug development.
The SMS-oncology team
Key factor aggressiveness pancreatic cancer might have been found
An important factor why pancreatic cancer can disseminate so rapidly has been discovered. Pancreatic cancer is one of the most aggressive types of cancer resulting in a high patient mortality rate. Metastases are formed at a very early moment in the development of the disease, often leading to a too late discovery of the cancer. Researchers of the Friedrich-Alexander-Universität Erlangen-Nürnberg (Germany) might have found the cause. They discovered that pancreatic cancer cells activate Zeb1, a key factor in the embryonic programme that controls how cells migrate and survive in early embryonic development. Zeb1 is blocked in fully developed cells, but is re-activated in cancer cells. With this reactivation the tumor cells now can spread throughout the body and easily adapt in new environments, resulting in metastases. Without the activation of Zeb1, cells can no longer easily adapt in a new environment, leading to a significant lower metastatic capacity. These findings can be used to develop new treatment strategies of pancreatic cancer and other aggressive tumor types. The paper was published in Nature Cell Biology.
Survival brain cancer patients extended with electrical stimulation
A new approach for the treatment of glioblastoma (GBM): data suggests electrical stimulation extends survival of patients with lethal brain tumors. A new technology called Optune administers low-intensity electric fields to newly diagnosed GBM patients who are treated with the chemotherapeutic drug temozolomide. It is thought that these electrical fields block the division of cancer cells. The study showed a median survival of 21 months compared to 16 months for those patients who only received chemotherapy. A 2-year survival of 43% versus 31% without the device was seen; for the 5-year survival this was 13% versus 5%. The study received considerable skepticism from some experts in the field, mostly regarding to lack of a control group. The researchers claim that a sham device is not possible, as the warmth normally coming from Optune would expose the placebos. The results have been presented at the AACR 2017 Annual Meeting, interim results were published in The JAMA Network earlier in 2015.
13% more pediatric cancer patients in the last 20 years
The global incidence of cancer amongst children has significantly risen in the past decades, according to data from the World Health Organization (WHO). Between 2001-2010, 140 per 1 million children under the age of 14 were diagnosed with cancer, which is a 13% increase compared to 1980-1990. The most common cancer type in this group is leukemia. Adolescents (i.e. up to 21 years old) were reported to have a cancer incidence of 185 per 1 million, of which the most common cancer type is lymphoma. It is likely that part of the reason for the rise is be better detection. The next step is to collect data from all over the world to establish all causes, which could include infections and environmental pollutants. In another investigation scientists looked more specifically to variation of survival from Acute Lymphoblastic Leukemia (ALL) and compared this between countries. Where the 5-year survival of children in Germany is 92%, this is only 52% in Colombia. However, ALL survival rates improved significantly in all countries. Comparing 1995-1999 to the same time span 10 years later, an increase from 79% to 89% in the UK and from 83% to 88% in the US was seen. Both papers were published in the Lancet Haematology.
Agios closes public offering over $250 million
Agios Pharmaceuticals raised $287 million in a new stock offering, as the cancer biotech nears potential FDA approval for its first drug enasidenib. The isocitrate dehydrogenase enzyme isoform mutations (IDH2m) inhibitor is a treatment for patients with Acute Myeloid Leukemia (AML). AML has an incidence of 5-8 per 100,000 individuals, but has a steep increase in the population aged over 70 years to 15-25 per 100,000 individuals. March 1st, Agios Pharmaceuticals announced that their leading drug has been accepted for review by the FDA and could obtain approval end of August. Enasidenib was granted priority review, meaning the application is based on data from a phase I/II study. Agios is expecting to also file for FDA approval of ivosidenib, another AML drug.
EMA / FDA
The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for:
- Inotuzumab ozogamicin (Besponsa, Pfizer) as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukemia (ALL). Patients with Philadelphia chromosome positive relapsed ALL or refractory B cell precursor ALL should have failed treatment with at least one tyrosine kinase inhibitor (TKI). The humanized anti-CD22 antibody was designated as an orphan medicinal product in June 2013.
- Two biosimilars of Mabthera: Riximyo (Sandoz) for the treatment of Non-Hodgkin’s Lymphoma (NHL), and Rixathon for the treatment of NHL and Chronic Lymphocytic Leukemia.
The CHMP adopted a positive opinion for the extension of:
- Bevacizumab (Avastin, Roche) in combination with carboplatin and paclitaxel for treatment of adult patients with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor–targeted agents. The monoclonal antibody is already approved in combination with carboplatin and gemcitabine for the same indications, as well as for other indications including subtypes of Colorectal Cancer (CRC), non-small cell lung cancer (NSCLC), Renal Cell Cancer (RCC) and Cervical Cancer.
- Nivolumab (Opdivo, Bristol-Myers Squibb) as monotherapy for the treatment of locally advanced unresectable or metastatic urothelial carcinoma in adults after failure of prior platinum-containing therapy. The anti-PD-1 monoclonal antibody is already available for the treatment of advanced Melanoma, NSCLC, advanced RCC, Classical Hodgkin lymphoma (cHL) and Squamous Cell Cancer of the Head and Neck (SCCHN).
The FDA granted approval for:
- Midostaurin (Rydapt, Novartis Pharmaceuticals) combined with standard cytarabine and daunorubicin induction and cytarabine consolidation for the treatment of adult patients with newly diagnosed AML who are FLT3 mutation-positive (FLT3+). The multikinase inhibitor is approved together with the the LeukoStrat CDx FLT3 Mutation Assay (Invivoscribe Technologies Inc.) as companion diagnostic to test patients with AML for the FLT3 mutation.
The FDA granted accelerated approval for:
- Brigatinib (Alunbrig tablets, Takeda Pharmaceutical) for the treatment of patients with metastatic anaplastic lymphoma kinase (ALK)-positive NSCLC who have progressed on or are intolerant to crizotinib. The tyrosine kinase inhibitor (TKI) was originally discovered by ARIAD Pharmaceuticals, which was acquired during development by Takeda Pharmaceuticals.
The FDA granted approval for the extension of:
- Regorafenib (Stivarga, Bayer HealthCare Pharmaceuticals) for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. The TKI is already approved for CRC and Gastrointestinal Stromal Tumors (GIST).