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Oncology Highlights - March 2018

Oncology Highlights - March 2018

Stay informed on the latest news within oncology drug development! Subscribe to our newsletter to keep up to date with last month’s science, industry and regulatory oncology highlights!

Enjoy reading! - The SMS-oncology team

Publications

ctDNA as liquid biopsy?

Circulating tumor DNA (ctDNA) offers an irresistible appeal in cancer biomarker development. It is a relatively inexpensive, liquid biopsy-based approach that can be potentially used to monitor a patient’s tumor burden and tumor molecular status, in a temporal and serial manner. In order to understand the present and future potential for use of the   technology in clinical practice, a joint expert panel from the American Society of Clinical Oncology (ASCO) and the College of American Pathologists conducted a literature review on the use of ctDNA assays. Key findings, from the selected 77 (out of a total of 1,338) research papers, were published in the Journal of Clinical Oncology (JCO). The panel’s initial recommendation is to be rather cautious when interpreting ctDNA assays. Clinical evaluation of ctDNA should be based on several aspects including, pre-analytical variables, analytical validity, clinical validity and clinical utility. The review indicates that plasma is the optimal specimen type for ctDNA analysis however further studies are required to address variables, such as specimen collection, handling, storage condition and time which might affect assay reproducibility. Analytical validity needs to be established for lower limit of detection of the assay, especially the optimal lower limits for detecting the various types of somatic variants. Clinical evidence suggests that the proportion of ctDNA in plasma varies substantially between patients and variant allele fractions of ctDNA can have potential prognostic and therapeutic implications. ctDNA assay have been shown to be more reliable at the time of disease progression rather than in early disease or while responding to prior therapy for advanced cancer. Importantly, in terms of monitoring therapy effectiveness, there is no current proof of clinical utility of ctDNA assays in this context. However, positive findings from approved ctDNA assays may be used to select a targeted therapy if the relevant genomic marker has demonstrated significant correlation when performed in tissue. The authors conclude that other than the well-validated assays with regulatory approval, most assays have insufficient evidence to demonstrate clinical validity, with also no evidence of clinical utility. The report recommends the integration of clinical information and available data from tumor analysis together with the ctDNA assay to select the appropriate therapy for patients. At the same time, the filed is rapidly evolving and evidence is continuously emerging that will support better evaluation of the clinical validity and utility of ctDNA assays.

European cancer mortality rates are predicted to decline for the past decade including 2018

In a recent compilation published in the Annals of Oncology, researchers predict the death rates in the European Union (EU) for most cancers will continue to fall this year, compared to 2012. The exceptions are cancers of the pancreas and lung in women, which will continue to rise. The data collected from WHO for stomach, colorectum, pancreas, lung, breast, uterus, ovary, prostate, bladder, leukaemia, and total cancers across EU indicates a regression by 10.3% in men between 2012 and 2018, and by 5.0% in women. This improvement in death rates in Europe comes in the absence of a single major breakthrough and is due to improved diagnosis and management of the disease. Prof La Vecchia who led the study explained the decreased risk with several factors such as the use of aspirin and oral contraceptives, hormone replacement therapy, effective screening and the availability of colonoscopy.

PET scan to identify PD-L1 responders

A new approach developed by Bristol-Myers Squibb allows scientists to image tumors bearing PD-L1, a biomarker of response to therapies known as PD-1 and PD-L1 immune checkpoint inhibitors. Using a radioligand fluorine-18 (18F) labelled anti–PD-L1 adnectin, researchers generated an image tracer called 18F-BMS-986192. The tracer showed selective binding affinity to tumors containing PD-L1 in mice and monkey studies. Researchers were able to visualize the PD-L1 expressing tumors in mice using PET imaging. The data indicated that the radioactive tracer is safe for humans. Currently, the ability to predict responders versus non responders depend on a single tumor biopsy. The new approach allows physicians to non-invasively assess all of a patient’s tumors for PD-L1 expression with a single PET scan through a temporal resolution of before, during, and after therapeutic intervention. Figure below: Maximal intensity projection images of kidneys and spleen 90 minutes post injection of 18F-BMS-986192 only (left) and of 18F-BMS-986192 and co-administration of 1 mg/kg BMS-986192 in the same monkey (center). Representative anti-PD-L1 immunohistochemistry of healthy monkey spleen tissue (right).

 

Industry

Immuno-oncology combination frenzy: Record breaking pact from Bristol-Myers

CAR-T expert Kite Pharma and the pioneer in zinc finger nuclease gene editing Sagamo Therapeutics announced their partnership to combine the proprietary cell-engineering strategies to develop next-generation autologous (patient-derived) cell therapies. Kite plans to use Sagamo’s zinc finger nuclease technology to establish the optimal gene editing platform for engineering T-cell genetic material. T-cell therapy involves modifying patient’s immune cells to go after specific targets. While this kind of immunotherapy can treat only one kind of cancer, the partners hope to develop specific treatments for several types.

EMA/FDA

EMA

The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for:

  • Trastuzumab (Kanjinti, Amgen) for the treatment of breast and gastric cancer. The biosimilar is a HER2 inhibitor monoclonal antibody similar to its reference product Herceptin.
  • Pemetrexed (Pemetrexed Krka, Krka) for the treatment of malignant pleural mesothelioma and non-small cell lung cancer. The generic disrupts folate-dependent metabolic processes essential for cell replication, and was approved without the need for a bioequivalence study versus the reference product Alimta; which was authorized in the EU since 20 September 2004.
  • Rucaparib (Rubraca, Clovis Oncology) for the treatment of relapsed or progressive ovarian cancer for its conditional approval. The PARP inhibitor was designated as an orphan medicinal product on 10 October 2012.

The CHMP recommended extensions of indications for:

  • Cabometyx (cabozantinib, Ipsen Pharma) for the treatment of advanced renal cell carcinoma (RCC) in treatment-naïve adults with intermediate or poor risk. The TKI was already approved for adults that received prior VEGF-targeted therapy.
  • Ivemend (fosaprepitant, Merck) for the prevention of nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy now also for paediatric patients aged 6 months and older, in addition to adults

  
FDA

The FDA granted regular approval for:

  • Nilotinib (Tasigna, Novartis) for the treatment of pediatric patients 1 year of age or older with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) or Ph+ CML-CP resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy. TKi was granted priority review and orphan drug designation and has been approved since 17 June 2010 for adult patients.
  • Brentuximab vedoti (Adcetris, Seattle Genetics) for the treatment of adult patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy. Approval was based on ECHELON-1 trial which showed 23% reduction in progression-free survival (mPFS) for combination therapy (Adcetris plus doxorubicin, vinblastine, and dacarbazine) versus bleomycin as a monotherapy.

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