Pembrolizumab, Larotrectinib Point to Future of Precision Medicine

Maurie Markman, MD


August 08, 2017

Hello. This is Dr Maurie Markman from Cancer Treatment Centers of America in Philadelphia. I want to briefly discuss two specific events that give us a great deal of information about the future of precision cancer medicine and the impact it's going to have on our patient population.

The first was the recent approval by the US Food and Drug Administration (FDA) of pembrolizumab for the "tumor-agnostic" treatment of patients with certain advanced metastatic cancers, including microsatellite instability–high (MSI-H) tumors. MSI-H tumors are known to have a lot of mutations within the cancer, suggesting the possible presence of neoantigens that might be favorably impacted by the checkpoint inhibitor. In fact, in data leading to the approval, objective response rates across the board in many tumor types were over 40%, with many of the responses lasting for long periods of time.

The second event was an abstract[2] presented at the 2017 annual American Society of Clinical Oncology meeting on larotrectinib, a selective tropomyosin receptor kinase inhibitor used for a very unusual situation affecting less than 1% of cancers. The hypothesis is that using this drug inhibitor in the presence of this abnormality might be very effective therapy. In a total of 46 pediatric and adult patients, involving 12 tumor types, an objective response rate of 78% was recorded, with many of these responses ongoing for long periods of time. This particular drug has not received FDA approval yet, but presumably, on the basis of the data presented and with additional patients collected, the agent will receive approval.


In one case, MSI-H is estimated to involve no more than 4% of cancer patients overall, and the second drug is estimated to involve 1% of cancer patients. This is clearly a small percentage of patients. But these two drugs may exhibit tremendous benefit and clearly make a very strong argument for the clinical utility of screening tumors for these abnormalities. It's almost certain that more such events are going to be reported in the near future.

This evidence and information provide overwhelming support for the importance of the process of precision cancer medicine and how it will potentially benefit our patients. This benefit may come in the near future in many cases. But in other cases it will be a longer journey before this process leads to drugs and strategies that will have that favorable impact we are all looking for. I thank you for your attention.


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