Jun 12 2022

Enemy On The Run?

by at 3:11 pm under Uncategorized

Greetings on a very rainy Sunday morning in the Philadelphia suburbs. We are at the new home of our son Ken and his wife, Sarah, ready to attend their daughters’ ballet recital at around noon. There is something very peaceful about being in a cozy home with lots of windows, watching it pour outside. Hopefully the rain will subside when we are ready to go to the recital, and from there, drive back to DC. This week’s blog is not about politics, insurrections or shooting wars. They are important, but today I want to write about progress that transcends conflicts.

I am still thinking about ASCO. By now, I can say comfortably that I avoided getting COVID-19, and it was a truly remarkable meeting. Last week, I described the game-changing findings regarding the use of a new HER2-targeted antibody-drug conjugate for women with HER2-low breast cancer. Upon further reflection, there was another, potentially even more revolutionary presentation.

A small study showed that treatment with an anti-PD1 antibody caused complete remissions of early stage mismatch repair-deficient rectal cancers in every treated patient. I repeat — every treated patient. This has profound implications, if verified in follow-up studies. The first implication is that immunotherapy with checkpoint antibodies can be applied to early stage rectal cancers with incredible efficacy, perhaps more so than in patients with more advanced disease. Conceivably, this could eliminate the need for surgery, radiation and chemotherapy one day, with immune memory preventing future metastases. Many of you know that the current rectal cancer standard of care requires surgery; if the cancer is too close to the anus, patients need AP resections that require a colostomy bag for waste elimination. The implications for both improved treatment outcomes and quality of life are no less than colossal. While I am hearing thunder from this morning’s rainstorm, perhaps it is an apt metaphor for the earth-shattering implications of this work.

A few words of caution: These are very preliminary data, and any changes to existing approaches that can be curative must be undertaken with the greatest of care, and only after rigorous clinical trials have been conducted and evaluated fully. Patients with mismatch repair-deficient rectal cancers are rare, and immunotherapy works well in such patients when their cancers have metastasized. This approach likely will not be as effective in cancers that are less sensitive to immune checkpoint inhibition. But now we have a blueprint. These findings provide an additional spark (as if one was needed) for a revolution in how we approach the therapy of rectal cancer, and down the road, who knows how many other types of malignancies.

How cool is it that we get a chance to contribute to a genuine revolution in cancer therapy? It does not always feel that way, but in the war on cancer, we are winning more battles, winning them decisively, and the enemy is on the run. ’Bout time…

Stay safe and be well.




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