RECENT ADVANCES IN PRECISION ONCOLOGY

Patients for Precision aims to share recent advances in cancer driven by precision oncology to demonstrate the wide range of potential benefits and to show how research in this field has the capacity to continually surprise the cancer community. Of course, clinical research studies need to be replicated and it takes many studies and much more to eventually impact standards of care.

Here are some recent examples of promising research results:

1. For thirty years there has been little progress for children with the most common form of brain cancer called a low-grade glioma. The standard of care with this pediatric cancer is to keep the tumor in check until the patient reaches age >20 when the tumor tends to regress and the patient survives. Chemotherapy and/or radiation are the typical options, but both can cause a lot of collateral damage. A recent clinical study of an experimental targeted therapy called tovorafenib has shown initial promising results in a small group of 22 children with a much larger clinical trial being launched shortly. Tovorafenib  targets mutations of a gene called RAF that is important in how cells grow and divide. Most kids with low-grade glioma show the RAF mutation via molecular testing. Clinical research is ongoing, but this targeted therapy could become a much safer alternative for children looking to beat this brain cancer. Ref: https://www.targetedonc.com/view/tovorafenib-demonstrates-early-positive-results-in-patients-with-plgg.
2. Recently reported results from a large clinical trial in metastatic breast cancer showed that Enhertu (trastuzumab deruxtecan), one of only a few approved antibody-drug conjugates (ADC), significantly extended the lives of patients with HER2-low metastatic breast cancer compared to standard chemotherapy. Like all ADCs the medicine works by having a monoclonal antibody deliver a cytotoxic agent more directly into cancerous cells. Patients on the drug survived an average of almost 24 months versus almost 17 months for those in the standard chemotherapy group, which according to specialists is unheard of in metastatic breast cancer research. If and when FDA approves the treatment for HER2-low patients, the expectation is that many more breast cancer patients will benefit from this kind of targeted therapy and research will begin to see if patients with earlier-stage disease might benefit too. (Ref: https://www.nytimes.com/2022/06/07/health/enhertu-breast-cancer-chemotherapy.html).
3. Surprising results were reported recently in a small Phase II trial of patients with locally advanced colorectal cancer whose tumors signalled mismatched repair deficiency and who were given an FDA-approved immune checkpoint inhibitor designed to prevent cancer from hijacking the body’s immune system to aid in its growth. The original idea for the study was to see if the immunotherapy medicine called dostarlimab could keep tumors in check or even shrink them enough to increase later chances of success with chemoradiation and surgery, which is standard practice for this type of cancer. Instead, the medicine worked so well after 6 months in all of the patients such that no cancer was detectable by any means (a complete response) and no patients had to go on to chemotherapy or radiation and surgery. Of course, small clinical trials like this will need to be replicated and the total length of the benefit determined, but thus far this is another promising result in cancer immunotherapy. (Ref: https://www.nytimes.com/2022/06/05/health/rectal-cancer-checkpoint-inhibitor.html.) and (https://www.nejm.org/doi/full/10.1056/NEJMoa2201445).
4. A recent study highlights the importance of increasing precision for the selection of patients who may be more likely to benefit from a standard treatment. Surgery is known to cure about 80 percent of stage II colon cancer patients, but cancer specialists also know that some will require adjuvant chemotherapy (after the surgery) to kill remaining residual disease. The problem is not knowing which patients and thus exposing many to chemotherapy unnecessarily. Recent research sheds light on the use of liquid biopsy to identify so-called circulating tumor DNA (ctDNA) that can be a measure of residual disease. Liquid biopsy means molecular-level testing using the peripheral blood of patients without the need for surgical tissue biopsy. In the stage II colon cancer clinical trial, ctDNA-positive patients were given the adjuvant chemotherapy and compared to another group given the adjuvant therapy but based on the usual method of measurement. The research found that by using ctDNA via liquid biopsy, around half of all patients could have been spared exposure to chemotherapy after their surgeries with absolutely no change in overall survival benefit. (Ref: https://www.nejm.org/doi/full/10.1056/NEJMe2204625).
5. KRAS (Kristen rat sarcoma viral oncogene homolog) is one of the most important biomarkers in cancer and although identified decades ago, was considered too elusive for targeting despite its important role in abnormal cell growth that leads to tumor formation. Lung, colon, and pancreatic cancers are most closely linked to KRAS mutations with approximately 30 percent of all lung adenocarcinomas in western countries having KRAS aberrations. The most frequent specific mutation is known as KRAS G12C. In 2021, the FDA approved the first-ever KRAS G12C targeted medicine called sotorasib for locally advanced or metastatic lung cancer with clinical results showing tumor shrinkage and progression-free survival with low levels of toxicity for patients in which standard chemotherapy or immunotherapy were not effective. Another KRAS G12C targeted therapy is also being tested in the clinic. Because KRAS mutated lung cancer is associated with a higher level of tumor aggressiveness and worse patient outcomes, the direct activity on KRAS G12C is a revolutionary development for precision oncology in lung cancer and these medicines are being tested in other cancers, as well (Ref: https://www.fiercepharma.com/pharma/amgen-s-lumakras-becomes-first-fda-approved-kras-inhibitor-for-lung-cancer-patients.)