Improved Survival with a Chemotherapy Free Option for EGFR Mutated Lung Cancer

Living with advanced non–small cell lung cancer (NSCLC) driven by mutations in the EGFR gene can feel overwhelming. For many patients, treatment has meant targeted therapy with the gold standard osimertinib, an oral targeted therapy directed toward the EGFR mutated tumor cells.  Data from the large MARIPOSA trial published in September 2025 in The New England Journal of Medicine has brought fresh hope: a chemotherapy free combination of two drugs, amivantamab plus lazertinib.  Together, this combination has shown a significant improvement in overall survival compared to the longtime standard, osimertinib.

This groundbreaking study included participants from Virginia Cancer Specialists research program and evaluated previously untreated advanced or metastatic NSCLC patients whose cancer has an EGFR mutation.  The study comparing three treatments:  the combination amivantamab plus lazertinib, osimertinib alone or lazertinib alone.

Amivantamab is a unique bi-specific antibody that targets two separate growth receptors that affect the survival of cancer cells, EGFR and MET. The blockage of both receptors prevents activating downstream signaling, thus shutting down the fuel that provides tumor growth.  This in combination with lazertinib, a third generation oral EGFR inhibitor, demonstrated significant improvement in survival, crosses the blood brain barrier and may help delay the onset of resistance mutations paving the way for a new standard of care.

Key Results: What Patients Should Know

• Patients getting amivantamab plus lazertinib had a significantly longer survival than those on osimertinib. The hazard ratio (HR) for death was 0.75 (95% confidence interval, 0.61 to 0.92; P = 0.005). A hazard ratio below 1 means lower risk of death. So, a HR of 0.75 means roughly a 25% reduction in risk of death for the combination therapy group
• At 3 years, about 60% of people treated with the combination were alive, versus 51% in the osimertinib group.
• The median overall survival was not yet reached in the combination arm at the time of analysis. In contrast, for those on osimertinib, the median OS was about 36.7 months.
• Although the combination has more side effects compared to osimertinib alone (including skin reactions, venous thromboembolism, infusion related events), no new safety concerns were uncovered in the study and these side effects were well managed.

Here’s what this could mean, for patients, families, and caregivers.

• Based on the way the data is pointing, median survival with the combo is projected to exceed one year longer than with osimertinib alone. In other words, patients might live more than a year longer, on average, with the combination

Chemotherapy-Free First Line Option

This is one of the first times a chemotherapy‐free combination has shown a survival advantage over a monotherapy targeted therapy in the first line setting for EGFR mutation positive lung cancer. That matters a lot because chemotherapy often brings additional side effects (nausea, hair loss, fatigue, immune suppression, etc.). For many patients, avoiding chemotherapy, or delaying it, means better quality of life while getting effective therapy.

Showing that amivantamab plus lazertinib not only improves progression‐free survival (i.e. how long the cancer stays controlled) but also extends life is a big leap. It suggests that targeting multiple pathways (EGFR and MET) together from the start, plus using a drug that penetrates the brain well can make a real difference. These differences are not just statistical, they translate into real additional months and years alive.

The Big Picture: Why Research Like This Is Imperative

• Improving overall survival (OS): Many studies in cancer show that a treatment delays progression (PFS), but fewer prove that it makes people live longer (OS). OS is the “gold standard” endpoint. This study did THAT. That’s rare and crucial. The only way to improve our patients’ outcomes is continued high quality and groundbreaking research.
• Targeted therapy evolution: EGFR mutations have been targeted via oral EGFR inhibitors as the gold standard for years. However, cancer adapts, and resistance develops, especially when therapy is given as monotherapy. By combining drugs that attack EGFR and another pathway (MET), researchers may delay or prevent resistance, leading to longer disease control and longer life.
• Reducing reliance on chemotherapy: Chemotherapy is effective but often comes with broader side effects. If we can treat with targeted drugs (or combinations) that spare patients from chemotherapy, that can mean fewer systemic side effects, better quality of life, and possibly better outcomes overall.
• Hope and quality of life: For many patients, surviving longer isn’t the only goal, it matters how one lives. Treatments that avoid or postpone severe side effects, maintain daily function, minimize hospital visits or toxicities, bring value in terms of quality of life. A chemotherapy free, targeted combination supports these goals and our patients.

What This Means for You and the Future

If you have EGFR mutated advanced NSCLC, amivantamab plus lazertinib offers a new treatment option that could extend your life significantly without the need for upfront chemotherapy. It may change the conversation you have with your oncologist.

Looking forward, this type of research underscores:

• The importance of mutational testing in all patients with advanced or metastatic lung cancer: knowing exactly which mutation you have allows for the most effective, personalized treatment.
• The need for continual efforts to design combinations that anticipate resistance rather than reacting to it.
• That living longer is becoming a more realistic outcome in many cancers; and we at Virginia Cancer Specialists, are striving to continue this trend while also focusing on quality of life and reduction in side effects.

Bottom Line

The MARIPOSA trial’s latest overall survival data show that for first line EGFR mutation NSCLC, amivantamab plus lazertinib is better than osimertinib alone with an approximate 25% lower risk of death with improved survival at 3 years (~60% vs ~51%). Importantly, this is achieved without chemotherapy, which could mean better tolerability and quality of life for many people.

If you or a loved one are facing EGFR mutated lung cancer, this is reason for cautious, hopeful optimism and a strong reason to discuss this chemotherapy free regimen with your care team.

Written by: Christina Brzezniak, DO

We here at Virginia Cancer Specialists are proud to be involved in this groundbreaking research.  In support of our local community we strive to bring access to the most advanced and state-of-the-art treatments for our patients, allowing them to remain right here in our community. We are seeing real progress in the evolution of cancer care, and here at Virginia Cancer Specialists, we will continue to care for our patients with these exciting new treatments.