Lung cancer is the leading cause of cancer death worldwide, affecting 1 in 16 people over their lifetime (Lung Cancer Research Foundation, 2024). Tragically, it also has one of the lowest survival rates, with only 27 out of 100 people expected to survive for at least five years after diagnosis (Modglin, 2024). While developing new treatments can take decades, we can make significant progress today by evaluating existing therapies in real-world settings. By analysing how current treatments perform outside of clinical trials, we can ensure that patients receive the best possible care immediately. Esther Dronkers, Programme Lead at LOGEX, discusses how this research is shaping the future of lung cancer treatment, ensuring that patients have access to the most effective therapies available.
So, there was a project in which real-world data of lung cancer patients were analysed?
Yes, the project, titled “The Effectiveness of Pemetrexed for NSCLC Patients,” was presented as part of a round table session of the Dutch Medication Audit (DMA). This initiative, led by the Dutch Institute for Clinical Auditing (DICA), a leading organisation specialising in clinical registries, involved a collaboration where DICA took the lead, MRDM handled data processing, and LOGEX provided data analytics and support.
What was the situation before the project?
For patients with metastatic non-small cell lung cancer (mNSCLC), the standard treatment traditionally consisted of pemetrexed combined with chemotherapy, followed by maintenance therapy with pemetrexed alone. Initially, pemetrexed was regarded as the most effective option for these patients.
However, the treatment landscape began to evolve in 2017, when the European Commission approved pembrolizumab (Keytruda), developed by Merck (known as MSD outside the U.S. and Canada), as a first-line therapy for mNSCLC patients whose tumors express high levels of PD-L1. The introduction of this immunotherapy opened new possibilities for patient care.
Following pembrolizumab’s approval, a keynote study demonstrated that the combination of pembrolizumab and pemetrexed was more effective than pemetrexed alone. As a result, clinicians adopted this combination therapy in their treatment regimens, leading to the question: Is pemetrexed still necessary, or could pembrolizumab alone be sufficient?
To address this, the DICA proposed investigating whether a real-world study could compare maintenance treatments involving pemetrexed, pembrolizumab, and chemotherapy. Clinical practices varied, with some hospitals continuing with combination therapy after the initial four cycles, while others chose to administer only pembrolizumab. The treatments continued until the patient either passed away, experienced disease progression, or was unable to tolerate the toxicity.
How was the data gathered and analysed?
The data was collected through the DICA medicine quality registry, which provided insights into current treatment practices.
One aspect we examined in the data was the approach hospitals took during the maintenance stage. Some hospitals never administered pemetrexed, while others always did.
We also explored whether we could demonstrate that one treatment approach was superior to another. We compared patients who received only one treatment to those who received both. However, because pemetrexed can be harsh on patients, those in poorer condition (e.g., with comorbidities or advanced age) often did not start with pemetrexed, complicating direct comparisons between the two groups.
To address this, we compared the policies of the hospitals. We selected hospitals with the most extreme approaches (either always administering or never administering pemetrexed) to determine if there was a difference in patient survival between the two groups. Within this initial study, we could not find a significant difference between the groups.
To strengthen the analysis, we re-examined the two patient groups. The data suggested that patients who did not receive pemetrexed had outcomes similar to those who did. However, further research is needed to confirm these findings and assess the broader implications of discontinuing pemetrexed as a maintenance treatment.
Why is this research significant?
During the roundtable session, we discussed that pemetrexed may not always be necessary as a maintenance treatment for mNSCLC patients. One oncologist mentioned that, based on the findings, he would now feel more confident stopping pemetrexed earlier than he typically would. This underscores the relevance of the DMA, roundtable discussions, and Real-World Data (RWD) in supporting evidence-based adjustments to clinical practice. The analyses will continue, and we are working towards a peer-reviewed publication to further explore and validate these insights.
Bibliography
Lung Cancer Research Foundation. (2024, 09 26). Lung Cancer Facts 2023. Retrieved from Lung Cancer Research Foundation: https://www.lungcancerresearchfoundation.org/lung-cancer-facts/#:~:text=1%20IN%2016%20PEOPLE%20will,and%201%20in%2017%20women.&text=Approximately%20127%2C070%20AMERICAN%20LIVES%20are%20lost%20annually.
Modglin, L. (2024, 07 15). Lung Cancer Survival Rates by Age: Key Insights. Retrieved from Patient Power: https://www.patientpower.info/lung-cancer/lung-cancer-survival-rates-by-age