buying time, and in some cases, buying enough time for other treatments
Among the hardest cases in oncology — lung cancer that has already reached the brain, the liver, or carries compounding genetic damage — a new pairing of two targeted therapies has offered something rare: measurable, meaningful extra time. Researchers presenting at the 2024 ASCO Annual Meeting found that combining amivantamab and lazertinib extended the period before disease progression by more than seven months compared to the current standard, with the greatest gains seen in patients who historically had the fewest options. The findings do not yet answer whether patients live longer overall, but they reopen a door that advanced EGFR-mutant lung cancer had largely closed.
- Advanced EGFR-mutant lung cancer almost always outsmarts its first treatment, leaving patients with poor options precisely when their disease is most dangerous.
- A secondary analysis of the MARIPOSA trial reveals that a dual-receptor antibody paired with an oral inhibitor cuts the risk of progression or death by 30 to 42 percent across the highest-risk patient groups.
- Patients with brain metastases, liver metastases, and p53 co-mutations — long considered the hardest to treat — saw the sharpest risk reductions, filling a gap that standard osimertinib therapy could not address.
- Median progression-free survival jumped from as low as 9.1 months on standard care to as high as 20.3 months on the combination, a shift that could redefine first-line treatment decisions.
- The critical question — whether living longer without progression translates into living longer, full stop — remains unanswered, and overall survival data will determine whether this becomes routine practice.
A drug combination is offering new hope to some of the most difficult-to-treat lung cancer patients — those whose tumors have spread to the brain or liver, or whose cancer carries additional genetic mutations that blunt standard therapies. Findings from a secondary analysis of the MARIPOSA trial, presented by Dr. Enriqueta Felip at the 2024 ASCO Annual Meeting, show that pairing amivantamab with lazertinib significantly outperforms the current standard treatment, osimertinib, in patients whose tumors carry EGFR mutations.
About 15 percent of non-small cell lung cancer patients carry this mutation. When their cancer advances or spreads, osimertinib is typically the first line of defense — but resistance almost always develops. Amivantamab takes a different approach, simultaneously blocking two tumor-driving receptors, EGFR and MET, while lazertinib adds a complementary oral attack. Together, they reduced the overall risk of disease progression or death by 30 percent, extending median progression-free survival from 16.6 months to 23.7 months.
The gains were even sharper among the sickest patients. Those with liver metastases saw a 42 percent risk reduction; those with brain metastases, 31 percent; those with p53 co-mutations, 35 percent. Across all high-risk groups, the combination extended progression-free survival by roughly six to seven months compared to standard care — a meaningful difference in a population with historically limited options.
Dr. Felip stressed that new strategies are urgently needed for these patients, particularly in early lines of treatment. Researchers are cautious, however: progression-free survival is not the same as living longer overall, and confirmation of an overall survival benefit will be essential before this combination can be widely adopted as a new first-line standard of care.
A new drug combination is showing promise for some of the sickest lung cancer patients—those whose tumors have already spread to the brain or liver, or whose cancer cells carry additional genetic damage that makes them harder to treat. Researchers presented evidence this week that pairing amivantamab, a monoclonal antibody, with lazertinib, an oral EGFR inhibitor, extends survival significantly longer than the current standard approach in these high-risk cases.
The findings come from a secondary analysis of the MARIPOSA trial, presented by Dr. Enriqueta Felip of Vall d'Hebron University Hospital at the 2024 ASCO Annual Meeting. The work focuses on a specific subset of lung cancer patients: those whose tumors carry mutations in the EGFR gene. About 15 percent of non-small cell lung cancer patients have this mutation, making it one of the most common genetic drivers of the disease. When the cancer is advanced or has spread, these patients typically receive a third-generation oral EGFR inhibitor called osimertinib as their first treatment. But the cancer almost always develops resistance, forcing doctors to search for alternatives.
Amivantamab works differently. It's a bispecific antibody that blocks two different receptors—EGFR and MET—simultaneously, attacking the tumor through multiple pathways. When combined with lazertinib, the pairing reduced the risk of disease progression or death by 30 percent compared to osimertinib alone. More strikingly, patients on the combination therapy survived without their cancer worsening for a median of 23.7 months, compared to 16.6 months in the standard-treatment group—a gain of more than seven months.
But the real story lies in what happened to the sickest patients. Researchers broke down the results by risk category: those with brain metastases, those with liver metastases, those carrying p53 gene mutations, and those with EGFR mutations detectable in circulating tumor DNA—essentially cancer cells floating in the bloodstream. In patients with brain metastases, the combination reduced progression risk by 31 percent. In those with liver metastases at the start of treatment, the risk dropped by 42 percent. Among patients with p53 co-mutations, the reduction was 35 percent. And in patients whose EGFR mutation appeared in blood samples, the risk fell by 32 percent. Across all these high-risk groups, median progression-free survival ranged from 16.5 to 20.3 months with the new combination, compared to 9.1 to 14.8 months with standard care.
Dr. Felip emphasized that these results address a critical gap. "In these cases, if the tumour is advanced or metastatic, new therapeutic strategies are needed, especially in early lines of treatment," she explained. The data suggest this combination could become a new first-line standard of care for metastatic or advanced EGFR-mutant lung cancer, particularly for patients with poor prognostic markers. However, researchers cautioned that longer follow-up is needed to confirm whether the progression-free survival gains translate into extended overall survival—the ultimate measure of whether patients live longer, not just longer without their cancer worsening. That question remains open, and it will shape whether oncologists adopt this approach as routine practice.
Citas Notables
In these cases, if the tumour is advanced or metastatic, new therapeutic strategies are needed, especially in early lines of treatment.— Dr. Enriqueta Felip, Head of Medical Oncology, Vall d'Hebron University Hospital
This new therapeutic combination offers superior benefits in patients with high-risk characteristics and could represent a new first-line standard of care for patients with metastatic or advanced non-small cell lung cancer with EGFR mutations.— Dr. Enriqueta Felip
La Conversación del Hearth Otra perspectiva de la historia
Why does it matter that this combination works better specifically in patients with brain or liver metastases?
Because those are the patients who have run out of good options. Once cancer spreads to the brain or liver, the prognosis darkens considerably. Standard treatment fails faster in these groups. A 42 percent risk reduction in liver metastases isn't just a number—it's the difference between months of additional time.
What makes amivantamab different from the drugs patients are already taking?
The standard drug, osimertinib, blocks one pathway. Amivantamab blocks two—it hits both EGFR and MET receptors. The cancer can't escape as easily when you're attacking it from two angles at once. That's why resistance develops more slowly.
Is this a cure?
No. It's an extension. Seven more months of progression-free survival is significant for someone with advanced cancer, but the disease still progresses. What matters is that we're buying time, and in some cases, buying enough time for other treatments to become available.
Why did researchers focus on these specific high-risk markers—p53 mutations, circulating tumor DNA?
Because those are the biological signatures of aggressive disease. If you can show benefit in the hardest cases, you've proven something real. It's easier to help a patient with a favorable prognosis. Helping the ones with p53 mutations or brain metastases—that's where the clinical value becomes clear.
What happens next?
They need to confirm that progression-free survival translates to overall survival—that people actually live longer, not just longer without their cancer worsening. That takes time. But if it does, this combination could become the first treatment doctors reach for in these patients.