February was short and cold: An opinionated take on NEJM highlights for February 2019

Targeted conjugated cancer therapeutics – so few, but may be more soon

The idea that one could combine the precision of a targeted biologic with the potency of a traditional cytotoxic to demolish a tumor has been around for decades, but with very rare exceptions, has not had the level of traction one would have expected.  But this month, the journal has two studies reporting on these types of therapies, both in breast cancer. One shows that in a group of heavily pre-treated triple-negative breast cancer patients, sacituzumab govitecan-hziy (Immunomedics) induced a respectable 33% response rate. The other shows that in HER-2 positive patients who have been operated but in whom there is residual disease (in the nodes), adjuvant treatment with trastuzumab-emtansine (Kadcyla, Roche) is superior to trastuzuman (Herceptin, Roche) with respect to freedom from recurrence. In a way both programs illustrate the dynamics at play: (1) conjugating a drug increases the complexity of the program, both from a PK/PD perspective and a CMC perspective (Immunomedics is currently embroiled in manufacturing issues with the FDA); (2) biologics on their own work pretty well, but as biosimilars start emerging from their long approval trek, one way for the incumbent to move the goal posts for their competitors is to seek incremental benefit with a conjugated modification.  Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer; Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer (subscriber access)


For medical nerds only: a new type of twins

Everyone knows that twins come in two flavors: identical and fraternal. Imagine the surprise of an ultrasound technician doing a prenatal scan of a woman pregnant with twins who shared the same placenta (indicative of identical twin) but with discordant sex!  Further genetic testing revealed that the twins had identical maternal genetic material, but seem to share only 78% of the paternal genome indicating fertilization with more than one sperm. By extension of the monozygotic and dizygotic twin nomenclature, the authors label this sesquizygotic twinning.  Molecular Support for Heterogonesis Resulting in Sesquizygotic Twinning  (subscriber access)


The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.

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