Lazcluze, Rybrevant Approval a ‘Big Deal’ for EGFR-Mutant NSCLC

Before choosing to receive Lazcluze and Rybrevant for EGFR-mutant NSCLC, it's important to consider the pros and cons.

Patients with EGFR-mutant non-small cell lung cancer (NSCLC) tend to do well on treatments, but eventually their disease may stop responding to therapies, highlighting a need for more treatments that help patients live longer without their disease progressing, according to Dr. Alexander I. Spira.

Data show that the recently approved combination of Lazcluze (lazertinib) plus Rybrevant (amivantamab-vmjw) can fill that need for patients with locally advanced (spread nearby) or metastatic (spread to other parts of the body) NSCLC that has an EGFR exon 19 deletion or exon 21 L858E substitution mutation.

Improved NSCLC Outcomes Are ‘A Very Big Deal’

“This [approval] is a very big deal,” Spira, co-director of Virginia Cancer Specialists Research Institute and director of the Thoracic and Phase 1 Program, said in an interview with CURE®. “Patients with EGFR mutations have actually always done very well with their treatments, but the reality is that the treatments do not last forever. The median duration of response in some of these therapies is still only about one to two years. These patients tend to be young and many of them want an aggressive treatment.”

The Food and Drug Administration (FDA) based their approval decision on findings from the MARIPOSA clinical trial, which included 1,074 patients who were randomly assigned to Lazcluze plus Rybrevant; Lazcluze alone; or Tagrisso (osimertinib), which is the current standard of care for this patient population.

Data from the combination and Tagrisso groups were published in the FDA’s announcement of the approval. They showed that the median progression-free survival (time patients live without their disease worsening) was 23.7 months for the Lazcluze/Rybrevant group compared with 16.6 months for the Tagrisso group.

At the time of data collection, overall survival — which describes the time patients live after treatment until death of any cause — was not yet ready.

Considerations Before Choosing Lazcluze Plus Rybrevant

Lazcluze and Rybrevant both work by targeting the mutated EGFR protein, which is involved in the growth and division of cancer cells. Tagrisso, conversely is a tyrosine kinase inhibitor — also known as a TKI — which is a type of drug that blocks tyrosine kinase enzymes which are also involved in the growth and division of cancer cells.

“[The combination] has been shown to be better than [Tagrisso] by itself,” Spira said. “But with that comes a price.”

Spira mentioned that Rybrevant is administered intravenously, which may not be as easy for patients as oral drugs that they can take at home, like Tagrisso or Lazcluze. However, researchers are currently investigating a subcutaneous (administered via an under-the-skin injection) Rybrevant.

Additionally, combining two drugs often comes with more side effects than with a singular drug, Spira mentioned. Most commonly, Lazcluze and Rybrevant can lead to rash, skin toxicity and diarrhea.

“It’s not for everybody, but for patients who can tolerate it — which is the majority of patients — and who are willing to put up with the additional infusion, there is an improved outcome from [the combination],” Spira said.

Looking Ahead in Lung Cancer Care

While Lazcluze plus Rybrevant provide a step forward in improving NSCLC outcomes, there is still more work to be done.

“We’d like to figure out if there is a sub-patient population that could benefit from the intensification of therapy?” Spira asked. “Then obviously the next step is finding better drugs. We've made a lot of headway, but the next step is to work and find better and better drugs for our patients.”

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