As clinicians and researchers seek targeted treatment regimens for patients with EGFR-mutated non-small cell lung cancer (NSCLC), an increasing number of clinical trials are investigating the effects of combination therapies. Two trials that have been in the headlines recently are the FLAURA-2 and MARIPOSA studies, which both led to FDA approvals of new front-line regimens in 2024.
The FLAURA-2 and MARIPOSA trials evaluated two distinct combination regimens. The FLAURA-2 trial assessed a combination of osimertinib and platinum-based chemotherapy versus osimertinib monotherapy. The MARIPOSA trial examined the efficacy of a combination of amivantamab and lazertinib versus osimertinib.
Both trials demonstrated improved progression-free survival (PFS) in the frontline setting. Additionally, a recent press release suggests that the MARIPOSA combination of amivantamab and lazertinib resulted in improved overall survival (OS) compared to osimertinib alone, though mature data has not yet been presented. Additionally, a trend toward improved OS was also observed in the FLAURA-2 trial when compared to osimertinib monotherapy.
“Certainly, an improvement in OS for either or both regimens is exciting news for patients and providers. How we will incorporate this into clinical practice I think remains to be seen,” said Susan Scott, MD, thoracic medical oncologist at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Sibley Memorial Hospital and Assistant Professor of Oncology at the Johns Hopkins University School of Medicine.
Although both FLAURA-2 and MARIPOSA demonstrated superiority over osimertinib monotherapy, they are each their own distinct combinations. Without a direct comparison between the two regimens, it remains unclear who will benefit the most from each treatment.
“Each new drug introduces new side effects. So, we would expect that a combination of amivantamab and lazertinib would have more side effects than osimertinib alone. We always have to balance these risks with the expected benefits, as well as consider patient and disease characteristics, along with patient goals and preferences,” Dr. Scott said. “There will be a population of patients who may be more interested in or could benefit more from a combination like amivantamab and lazertinib. There may be others that benefit more from a combination of osimertinib and chemotherapy.”
The evolving landscape of combination treatments offers patients a wider array of options and aims to facilitate more personalized regimens.
“I’m still reviewing additional data to determine which combination regimen is best for high-risk patients. I hope we will gain more insights on this during the coming years. It’s always good to have options, and I believe treatment is an individualized decision,” Dr. Scott said. “Some of it comes down to patient preferences, their risk factors for additional combination therapies, and specific disease features that may lean me toward one or the other.”
So, with these recent findings from FLAURA-2 and MARIPOSA, does this mean the end of osimertinib monotherapy? Not necessarily, she said. The decision largely depends on assessing the patient’s preferences and needs regarding treatment schedule, goals, and logistics.
“I consider all three regimens when I see a patient with newly diagnosed EGFR lung cancer. A patient who seems to have low risk disease features, or is averse to combination therapies due to the additional toxicity and risks that come with that. That would be a patient I would consider appropriate for osimertinib monotherapy,” Dr. Scott said. “I’m considering combination therapies more and more, particularly for patients with brain metastases, those with positive ctDNA at diagnosis, patients with a high burden of disease, or those who are very symptomatic.”
While the data on combination regimens from FLAURA-2 and MARIPOSA is promising, additional research is needed to identify who can safely receive osimertinib as monotherapy. Furthermore, greater precision is required to differentiate between the two combination regimens.
“Additional studies are needed to examine these higher-risk subgroups, ideally comparing the regimens,” Dr. Scott said. “I know that’s a big ask in the frontline setting when both regimens are approved. But hopefully that data will be available in the coming years as we gain more experience with these different regimens.”
