The outlook is hopeful

Doctor Kristof Cuppens

Interview with Dr. Kristof Cuppens

Information is being exchanged globally, and many excellent research groups are actively contributing. The bar is consistently raised, and the prospects of scientific research are promising.

Dr. Kristof Cuppens (Jessa and Sint-Trudo Hospital) is a pulmonologist specializing in oncology and is involved in international research on personalized medicine and immunotherapy.

Can you explain your research?

In recent years, the success and survival rates of lung cancer treatments have significantly improved, especially due to progress in two key areas: immunotherapy and personalised medicine. 

A medication intervention in immunotherapy causes the immune system to be activated. The tumor is recognized and attacked. This has become a corner stone in most treatments for lung cancer.

Additionally, personalized medicine seeks to identify treatable errors in the genetic material of the tumor. The technical term for these errors is AGA, actionable genomic alteration. To clarify: this has no connection to heredity or communicable diseases. Tumors arise from uncontrolled cell growth. Each new cell is equipped with building blocks ("genetic material") to facilitate further growth. The genetics of a tumor can include one or more errors that cause cells to grow excessively and rapidly. Sometimes, this is driven by a specific, dominant abnormality. Identifying this abnormality as the causal error for uncontrolled growth theoretically enables targeted treatment. In every lung cancer diagnosis, biopsies are now routinely examined not only to identify the type of lung cancer but also to detect these errors. We specifically search for errors that may have a corresponding targeted treatment available. In recent years, an exponential number of these errors have been identified and mapped. For many mutations, there are now targeted medications available.

In lung cancer, for example, targeted testing is conducted for EGFR and ALK abnormalities, which occur in 10% and 5% of patients, respectively. Approved medications are available for these abnormalities, and the more targeted the treatment, the higher the success rate and the greater the impact on disease progression. There are also abnormalities that occur even less frequently but are treatable with approved medications. Advances in detection methods and improved understanding of tumor genetics are enabling the identification of increasingly rare targets. For many of these abnormalities, medications are still in the research phase, creating overlap with clinical studies. It is crucial to connect eligible patients with these opportunities.

"In 20% of cases, a "blind" chemotherapy treatment is initiated instead of a targeted approach."

Biopsies are, understandably, not popular among patients, but unfortunately, given the impact of genetic testing, sometimes - especially when a genetic abnormality is highly suspected - more than one biopsy is needed. A Belgian study shows for EGFR that patients and physicians do not always await the outcome of that testing. There is a tension: the concept is well known, yet in 20% of cases one does not initiate targeted but "blind" chemotherapy treatment. However, the waiting time after biopsy is perfectly within international standards in our country: on average 5 to 10 working days after taking the biopsy, the result is known. It is important to communicate this so that people wait for the biopsy results. After all, targeted treatment usually yields very impressive results, greatly increasing the chances of success. This is more sustainable in the long run than a blind approach.

New elements are constantly being discovered. Will we ever find a treatment for everything?

I don't think so. A "one size fits all" approach will never be possible. In non-smokers, the condition can often be treated with a targeted approach. However, in smokers or those exposed to carcinogenic substances, the genetic material tends to show many more abnormalities, making treatment more challenging. You could compare an AGA tumor to the slave ship in Asterix and Obelix—everyone rows at the same pace. But a tumor caused by carcinogenic substances is pure mutiny; eliminating one factor doesn't halt the growth. In these cases, a more agnostic approach, such as chemotherapy and/or immunotherapy, may work better.

You were also involved in a study on combination immunotherapy?

The NEOpredict lung study included patients with operable lung cancer. Often, lung cancer patients require chemotherapy after surgery, especially when tumors are larger or involve lymph nodes. This study administered a short course of immunotherapy or a combination of two immunotherapeutics before surgery, lasting “only” four weeks. The research aimed to determine whether this approach could be done safely without jeopardizing the life-saving surgery and whether it could lead to “tumor death,” potentially reducing the need for post-surgery treatment.

"If we can better identify patients, we can offer them more personalized, targeted immunotherapy."

In recent years, the approach to operable lung cancer has become much more aggressive, with a combination of chemotherapy and immunotherapy administered over 9 to 12 weeks before surgery. This approach indeed achieves a very high pathological response rate (up to 45%) and significantly reduces the risk of postoperative recurrence. However, 15% to 20% of patients are unable to proceed to surgery due to the heavy treatment regimen and disease progression. In our study, we demonstrated that a short course of immunotherapy, using mono- or combination therapy, is very safe, with all patients able to proceed to surgery. Additionally, we observed promising results, with more than 30% achieving a pathological response.

That's why we're going to investigate whether it’s possible to predict in advance whether immunotherapy will work based on laboratory tests. This is the bridge to personalized medicine or personalized immunotherapy. Additionally, we’re exploring whether we can streamline treatment to create a chemo-free or chemo-reduced option. If we can better identify patients, we can offer them more personalized, targeted immunotherapy. We expect to publish new data on this in the second half of 2025, completing another piece of the puzzle. The outlook is hopeful.