Publication
Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC
Amivantamab plus lazertinib (amivantamab–lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated...
What is it about?
This summary outlines the findings of the MARIPOSA phase 3 study that evaluated the efficacy and safety of amivantamab plus lazertinib, as compared to osimertinib, in adult patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) that has specific mutations in the epidermal growth factor receptor (EGFR) gene (exon 19 deletions or exon 21 L858R substitution mutations). The study included 1074 patients who had not been treated before. Patients with asymptomatic or stable brain metastases were eligible to enroll. Patients who had not received prior treatment were randomized into three groups: one group received the new drug combination (amivantamab plus lazertinib, n=429), another group received osimertinib (n=429), and a third group received lazertinib alone (n=216; this non-registrational lazertinib arm was included to study the contribution of components). The effectiveness of the treatment was primarily measured by the time when half of the patients in the study lived without their cancer growing or spreading since they started the treatment. Results from the study showed that patients who received amivantamab plus lazertinib lived longer without their cancer growing or spreading compared to those who received osimertinib (23.7 months vs. 16.6 months, respectively). The most common adverse reactions (≥20%) were rash, nail toxicity, infusion-related reactions, musculoskeletal pain, stomatitis, edema, venous thromboembolic (VTE) events, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin, decreased sodium, increased alanine aminotransferase (ALT), decreased potassium, decreased hemoglobin, increased aspartate aminotransferase (AST), increased gamma-glutamyl transferase (GGT), and increased magnesium.
Why is it important?
Real-world data highlights patients with advanced NSCLC with EGFR mutations have a 5-year survival rate of 19%. Additionally, 25% to 40% of these patients may die before they can receive second-line therapy. The findings of this study present a potential first-line treatment option for patients with EGFR-mutated (exon 19 deletions or exon 21 L858R substitution mutations) advanced NSCLC. Key Takeaways:
Amivantamab plus lazertinib extends the time without disease progression more effectively than osimertinib. The median amount of time that patients lived without their cancer growing or spreading was 23.7 months in the amivantamab plus lazertinib group compared to 16.6 months in the osimertinib group (hazard ratio [HR], 0.70; 95% confidence interval [CI]: 0.58-0.85; p=0.0002). At 18 months, 60% of patients receiving amivantamab plus lazertinib were alive without their cancer growing or spreading, compared to 48% of patients on osimertinib. At 24 months, 48% of patients in the amivantamab plus lazertinib group were alive without their cancer progressing or spreading, compared to 34% of patients in the osimertinib group. Patients who had a history of cancer that had spread to the brain and received amivantamab plus lazertinib were observed to have a longer time without disease progression. The median amount of time that these patients lived without their cancer growing or spreading was 18.3 months in the amivantamab plus lazertinib group compared to 13.0 months in the osimertinib group. Patients with high-risk disease characteristics, such as detectable circulating tumor DNA at baseline and during treatment, TP53 co-mutations, and baseline liver or brain metastases, may have poor treatment outcomes. However, a secondary analysis from the MARIPOSA study revealed that some of these patients showed improved treatment outcomes when treated with amivantamab plus lazertinib, compared to those treated with osimertinib.
The most common adverse reactions (≥20%) were rash, nail toxicity, infusion-related reaction, musculoskeletal pain, stomatitis, edema, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, and increased magnesium. Serious adverse reactions occurred in 49% of patients who received amivantamab in combination with lazertinib. Serious adverse reactions occurred in ≥2% of patients, including VTE (11%), pneumonia (4%), rash and interstitial lung disease (ILD)/pneumonitis (2.9% each), COVID-19 (2.4%), and pleural effusion and infusion-related reaction (2.1% each).
Genetic Testing Importance: Early genetic testing for EGFR mutations can guide the selection of effective treatments and may help improve patient outcomes.
