Two reports from the June 2022 meeting of the American Society of Clinical Oncology (ASCO) have generated great excitement and reporting by the New York Times and multiple media. The most important cancer meeting of the year was attended by 30,000 oncologists and the attention was overwhelmingly given to the new development in the treatment of rectal cancer. However, the discovery in the treatment of a certain variation in breast cancer will help many more people.
The report from Memorial Sloan Kettering Cancer Center (MSK) involved the treatment of patients with Stage II or III cancer of the rectum that is cancer limited to the rectum but with invasion of the lining of the rectum. Most importantly the patients involved in the study had a condition known a mismatch repair deficiency. In this condition the patient’s cells cannot fix errors in DNA that occur as cells grow and divide. Over time these cells develop many mutations and become susceptible to developing certain kinds of cancer that are sensitive to attack by the immune system. The problem is that the immune system often cannot kill the cancers because the cancers develop a protective covering called PDL1. We now have treatment that can block PDL1 and allow the immune system to destroy the cancer.
Because the number of patients with mismatch repair deficiency is low, fewer than 10% of patients with rectal cancer have this condition. Only 14 patients were included in this report. OVER 90% OF RECTAL CANCER PATIENTS DO NOT HAVE THIS CONDITION AND THE REPORT DOES NOT APPLY TO THEM OR OTHER CANCER PATIENTS WITHOUT MISMATCH REPAIR DEFICIENCY. Nevertheless, it is exciting to see that using an agent which blocks PDL1 allows the immune system to completely destroy the cancers in these patients without any radiotherapy or surgery. This is extremely meaningful for this small group of patients.
The other exciting report from ASCO involves many patients with breast cancer, perhaps as many as 60% of breast cancer patients. A protein known as Her2neu on the surface of many breast cancer cells can drive the cancer. It has been known for over 20 years that cancers that over express Her2neu respond well to treatments that bind to and inactivate Her2neu. Patients who did not over express Her2neu were not treated with these agents.
This ASCO presentation showed that even a low-level expression of Her2neu would respond dramatically to a drug called trastuzumab deruxtecan. The patients in this study had already received chemotherapy for recurrent breast cancer. Half were treated with chemotherapy and half with trastuzumab deruxtecan. Patients had twice the disease-free survival and lived 5 months longer than patients who received chemotherapy. This study has the potential to change our treatment recommendations for a large number of patients. We might anticipate that after more studies it may be used much earlier in the disease with possibly profound effects on cure rates. Trastuzumab deruxtecan does have significant side effects particularly on the lungs so we will wait on further studies to ensure the safest treatment protocols have been fully vetted.
As oncologists, we are thrilled to learn of these advances in the science of treating cancer, one with the potential to help a good number of those diagnosed with breast cancer and the other, a much smaller, but specifically targeted, variation of rectal cancer.