Post-Progression and Safety Outcomes With First-Line Amivantamab Plus Lazertinib vs Osimertinib for Advanced NSCLC: Best Management Practices

Sarah Smith, BD, CNMT, Virginia Cancer Specialists, Fairfax, Virginia, discusses findings from the phase 3 MARIPOSA study exploring post-progression and safety outcomes with first-line amivantamab plus lazertinib vs osimertinib for advanced NSCLC and offers guidance for best management practices. These findings and guidance were presented at the 2024 Oncology Nursing Society (ONS) Congress in Washington, DC.

Transcript:

Hello! My name is Sarah Smith. I'm a clinical research coordinator at Virginia Cancer Specialist in Fairfax, Virginia. Thank you for having me today. I'm pleased to discuss some of the key points from our recent study presented at the 2024 ONS Congress, titled Post-Progression and Safety Outcomes With First-Line Amivantamab Plus Lazertinib vs Osimertinib in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) With Common EGFR Mutations: Implications for Best Management Practices.

What led you and your colleagues to conduct this study?

Patients with advanced NSCLC and common activating mutations in the EGFR gene are unfortunately faced with limited treatment options, high mortality rates, and can often experience disease progression with first-line treatments due to various resistance mechanisms. Given these challenges, there's a need for new therapies for this group of patients.

Amivantamab is an EGFR and MET receptor directed by specific antibody currently approved for treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, both as a single agent after progression on platinum chemotherapy and in a combination with chemotherapy as a first-line treatment.

Initial results from the global MARIPOSA study demonstrated that amivantamab plus lazertinib, which is a third-generation, brain-penetrant, oral, EGFR tyrosine kinase inhibitor, significantly reduces the risk for disease progression or death when compared with third-generation EGFR inhibitor osimertinib alone in patients with treatment-naïve NSCLC and common EGFR mutations.

However, it is important to note that treatment with these EGFR inhibition therapies can often result in off-target effects, such as infusion-related reactions, dermatological events, including rash and paronychia, soon after treatment initiation, generally seen within the first 4 months.

If not managed appropriately and pre-treatment education is not offered, such adverse events can greatly impede the patient's experience, resulting in poor treatment adherence, treatment interruptions, and discontinuation.

In addition, despite the efficacy of amivantamab plus lazertinib, some patients will still experience disease progression, requiring treatment intensification, and thus increasing the risk of further adverse events. In the clinical setting, nurses and healthcare professionals play a crucial role in the proactive management of these adverse events. Educating patients on the possibility of progression, dealing with intensification-related adverse events, implementing prophylactic measures, and emphasizing to the patients the overall benefit of treatment adherence, especially to the first-line treatment.

The goal of the study was to present additional post-progression efficacy and safety outcomes from the MARIPOSA study and to provide a clinical perspective on the key role. nurses play in patients’ experience alongside some of the best management practices.

What were the study methods?

MARIPOSA was a randomized multicenter phase 3 study that enrolled aged 18 years or older patients with treatment-naïve locally advanced or metastatic NSCLC and documented common EGFR mutations.

Eligible patients were randomized to receive either amivantamab plus lazertinib, osimertinib alone, or lazertinib alone. The lazertinib treatment arm was included to assess contribution of each treatment component. However, we did not present that in our poster at the ONS Congress.

This study looked at key post-progression outcomes, including time to treatment discontinuation, time to subsequent therapy, duration of treatment beyond progression, subsequent therapy and therapy class, and finally, safety outcomes, such as the key onset of adverse events as previously mentioned, including rash and paronychia.

In addition, implications and best practices for disease progression and adverse events management were gathered based upon my own clinical experience, as well as interview responses from 2 other clinical oncology nurses.

Can you summarize the post-progression findings?

There were a total of 421 patients in the amivantamab plus lazertinib arm and 428 patients in the osimertinib arm that were included in the analysis.

After a medium follow up of 22 months, 35% of patients receiving amivantamab plus lazertinib vs 47% of patients receiving osimertinib had disease progression. About half of the patients in each group with progressive disease continued treatment beyond initial progression. The median duration of treatment beyond this initial disease progression was 23.6 weeks in the amivantamab plus lazertinib arm vs 15.9 weeks in the osimertinib arm.

Both treatment time to discontinuation and time to subsequent therapy were numerically longer in patients receiving the amivantamab plus lazertinib vs osimertinib and overall, a lower proportion of patients discontinued study treatment when receiving the amivantamab plus lazertinib vs osimertinib.

Among those patients who did discontinue study treatment and receive subsequent therapy, the most common therapy was a doublet chemotherapy.

The median duration of exposure for patients receiving amivantamab plus lazertinib was 18.5 months, however, most key adverse events occurred within the first 4 months, as mentioned previously. And that was based on treatment initiation and late onset was very uncommon.

Most key adverse events experienced by patients were manageable in the study.

What were some key nursing perspectives identified in the study?

As mentioned previously, nurses and other healthcare providers play a crucial role throughout the patient journey, and they offer a comprehensive and multidisciplinary care to optimize the patient experience.

We identified 4 key areas which nurses and other healthcare providers contribute to promote optimal patient experience. These included counseling, patient education, adverse event management, and treatment navigation. For example, patients may relate more to nurses, just due to the close interactions which provides an opportunity to promote healthy communication, hold empathetic conversations, discuss patient goals, all while providing support and comfort through the entire treatment journey.

Given the knowledge of nurses and other healthcare professionals, the benefit of sharing information and educating patients using lay language should also be emphasized here. Educating patients on their treatment plans, expected medications, what adverse events are likely to occur, and when they're likely to occur, how to manage these adverse events efficiently, and being transparent on the risk of disease progression can help ease the patient concerns during treatment. Furthermore, adverse events can occur early during treatment and may challenge your patients’ willingness to continue therapy, so being proactive is very key.

Nurses and other healthcare providers can help identify patients in need of evaluation or treatment for specific adverse events and help determine the best prophylactic management to help mitigate these adverse events. By managing adverse events, nurses and other healthcare providers can help promote appointment attendance and treatment adherence, thus optimizing the clinical outcomes of the patient.

If a patient experiences disease, progression and begins intensification, therapy the healthcare providers and nurses should help guide them through the next step while preparing them for the management of the common intensification, related adverse events.

But all in all, the contribution of the nurses and other healthcare providers are multifaceted. Given the known clinical benefit of staying on treatment, these providers play a crucial role in managing and supporting patients throughout the various challenges they may face, such as the occurrence of these adverse events.

What key takeaways from the study would you like to highlight?

Overall, in the phase 3 MARIPOSA study, patients receiving amivantamab plus lazertinib remained on treatment longer and exhibited favorable post-progression outcomes when compared to patients receiving osimertinib alone. Thus, representing a viable first-line option for patients with advanced NSCLC and common EGFR mutations.

The key onset of the adverse events as mentioned, such as the dermatological, occurred within the first 4 months of treatment initiation, thus highlighting the importance of prophylactic and just a proactive measure for early intervention.

As identified in the study, some of the vital roles of nurses and healthcare providers include the management of these adverse events, providing patient information on potential disease progression, remaining clear about the additional adverse events associated with post-progression treatment intensification. And finally, incorporating perspectives surrounding the optimal adverse event, management and improved patient experience can positively impact treatment adherence which ultimately is the key for ensuring improved outcomes, not only in first line but also in the post-progression setting.