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German Initiative Making Headway in Improving Lung Cancer Patients' Precision Oncology Access

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NEW YORK – A German precision medicine initiative, called the national Network Genomic Medicine (nNGM) Lung Cancer, has made significant headway over 10 years in improving lung cancer patients' access to molecular profiling and precision medicine, according to one of its founders.

The nNGM program is based out of the Center for Integrated Oncology at the University Hospital Cologne and is an extension of a genomic medicine initiative that began at the hospital in 2010. Founded by three professors there — Reinhard Büttner, Jürgen Wolf, and Roman Thomas — it has been funded by the nonprofit German Cancer Aid since 2018. Last month, Büttner, Wolf, and Thomas won the German Cancer Aid Prize for their work on the nNGM and its efforts to advance molecular diagnostics and precision treatment in lung cancer.

The network includes 28 centers where an estimated 60 percent of lung cancer patients in Germany receive care, according to Büttner, who is also director of the Institute of General Pathology and Pathological Anatomy at University Hospital Cologne. Currently, the network performs testing for about 17,000 lung cancer patients each year in Germany.

"With the growing network, we now see stage IV lung cancer patients that have reached 10 years of survival and have very good quality of life," Büttner said. "Some of these patients are highly engaged [after being part of the network], and they want to learn everything about lung cancer. Now, we have a group of patients in our network that speak to us at an equal level, that are our partners rather than our patients."

The network has two aims: to provide molecular diagnostics and analysis to patients at network hospitals and to use patients' data from these tests to further lung cancer research.

For the diagnostics service, the network hospitals work with smaller hospitals and clinics to facilitate molecular profiling. Büttner noted that many lung cancer patients in Germany are being diagnosed and treated at these smaller clinics that don't typically have access to the same sequencing technology available at the larger network hospitals.

The network hospital liaisons try to obtain a sample from lung cancer patients treated at local healthcare facilities for comprehensive molecular profiling, including testing on a large DNA sequencing panel, a large RNA sequencing panel, and immunohistochemistry. The results are then considered by a multidisciplinary molecular tumor board, which makes therapy recommendations based on test results.

"The actual therapy is then provided by the local oncologist," Büttner said. "That made the network more acceptable [to these smaller groups] because the clinical partners do not fear that they will lose patients, and they don't have to send the patient to another hospital."

One goal of the network is to facilitate molecular testing when patients' tumors are still in early stages and more treatable. The group typically flags lung cancer patients for molecular testing when they are newly diagnosed with advanced disease. Other efforts to provide centralized molecular profiling in Germany test patients only after they have received all approved therapies, but Büttner believes that is too late to make much difference in outcomes.

"Every tumor should be profiled in the beginning" he stressed, adding that nonselective therapies for lung cancer, like chemotherapy, can create genomic rearrangement and heterogeneity in tumors that make targeted therapies less effective in heavily pretreated, later-stage tumors.

To that end, nNGM partners recently considered whether patients treated in the network had improved survival versus patients who were not part of the program. In a recent publication, the researchers reported a significant survival benefit for the nNGM patients, who had a median overall survival of 10.5 months versus 8.7 months in the non-nNGM group. The nNGM group also used more tyrosine kinase inhibitors in the first-line setting, where several available treatments target molecular biomarkers driving the tumor, compared to the non-nNGM patients — 8.4 percent versus 5.1 percent, respectively.

"When we started the network 10 years ago, the most common reaction from oncologists I heard was that we have these effective platinum therapies. [They wanted to] do this first and then keep the [molecular profiling] information to the very end," he noted. "We should know [a tumor's molecular profile] at day zero before the first-line therapy. It's important we convince [providers] in my country who still believe that targeted therapy is something to keep in the back of my head at the very end."

In the US, oncologists are also steadily recognizing the value of molecular profiling cancer patients when they're in the early stages of the disease. A Precision Oncology News survey of 20 cancer centers and hospitals in the US found that in 2023, stage I/II patients were being offered molecular testing at 14 institutions, or 70 percent, versus 30 percent of programs offering stage III/IV cancer patients such testing. In comparison, in 2022, 55 percent said stage I/II patients were being offered molecular testing at their institutions, and 45 percent said patients were offered testing only in more advanced stages.

The other aspect of precision medicine-focused projects is to improve the field's understanding of the biology of cancers and spur clinical trials that test the activity of drugs and tests that apply that knowledge. Toward that end, the nNGM has generated many publications and clinical trials that explore the prevalence of certain lung cancer mutations, the effect of mutations on patients' outcomes, and the activity of novel medicines. The network has six task forces focused on advancing different areas of precision medicine: molecular diagnostics; quality assurance of molecular diagnostics; digital networking and data collection; molecular tumor boards and preclinical evaluation; clinical studies; and genetic tumor risk.

The nNGM task forces are largely responsible for standardizing and harmonizing diagnostics processes, data collection, molecular tumor boards, and preclinical and clinical trial designs across the network.

"For example, there is one task force that guarantees homogeneous mutational detection," Büttner said. "Different centers may have different reference genomes, so we don't want one center calling an EGFR mutation in, let's say, codon 718 and the next one calls it codon 719. It can cause a lot of confusion." To avoid such confusion, within the nNGM, there is one task force that makes unified sequencing variant calls and makes consensus therapeutic recommendations, he noted.

The network also facilitates clinical trials at its network hospitals. In one study, data from which was published in December, researchers explored the outcomes of PD-L1-high NSCLC patients on first-line treatment with Merck's checkpoint inhibitor Keytruda (pembrolizumab) based on their KRAS and TP53 status. Nearly 700 patients had their tumors sequenced and received treatment within this nNGM trial. The researchers found that high PD-L1-expressing NSCLC patients with KRAS G12C/TP53 co-mutations had the best long-term survival rates on Keytruda.

Büttner also highlighted a recently initiated study exploring concurrent, asynchronous sequencing of germline mutations using liquid biopsy and whole-exome sequencing of tumor biopsies to identify genetic variants that may increase a patient's risk of lung cancer. From this research, the network hopes to identify any variants that confer higher lung cancer risk and potentially develop an early detection program for these patients with other German healthcare providers.

"The research and trial activity in the network strengthens the unity of the network centers because every site, every researcher, every oncologist, every pathologist can be engaged in a research project," Büttner said.

Going forward, Büttner hopes the network will continue to grow and strive toward its goal of making precision medicine available to all lung cancer patients in Germany. To do so, Büttner said the network will need to partner with more large academic hospitals, so it can expand its molecular profiling capabilities and reach even more patients around the country at the smaller, regional hospitals or clinics.

One day, he hopes the network will be able to provide precision medicine-supportive services for patients with other tumor types. But for now, the group is focused on filling the need in lung cancer and empowering more patients to advocate for themselves.

"These patients now engage with politicians, [and] they talk to their healthcare providers to advocate for better care," Büttner said. "They talk [for] the scientific community and say that these people need money for their research. That changes the atmosphere in oncology. They can help move the field, and they are authentic propagators of precision oncology. That is something new, and that is something I am really happy about."