Lazertinib (1) – Lazcluze®
Non-small cell lung cancer, EGFR exon 19 deletions or exon 21 substitution mutations (L858R), combination with amivantamab
Characteristics
| Start date | 15.02.2025 – Marketing authorisation: 20.01.2025 |
|---|---|
| Resolution | 17.07.2025 |
| INN | Lazertinib |
| Brand name | Lazcluze® |
| Pharm. company | Janssen-Cilag GmbH |
| G-BA Procedure ID | D-1165 |
| ATC code | L01EB09 EGFR tyrosine kinase inhibitors (L01EB) |
| ICD-10 codes (AIS) | C34.0Malignant neoplasm of carina, C34.1Malignant neoplasm of upper lobe, bronchus or lung, C34.2Malignant neoplasm of middle lobe, bronchus or lung, C34.3Malignant neoplasm of lower lobe, bronchus or lung, C34.8Malignant neoplasm of overlapping sites of bronchus and lung, C34.9Malignant neoplasm of unspecified part of bronchus or lung |
| Alpha-ID codes (AIS) | I111155Carcinoma of the upper lobe bronchus, I116693Non-small cell lung cancer, I24595Carcinoma of the main bronchus, I30015Lung carcinoma of the middle lobe, I30021Lung carcinoma of the lower lobe, I30022Malignant neoplasm of the bronchi and lungs, overlapping several sub-areas |
| Therapeutic area | Oncological diseases Non-small-cell lung carcinoma (NSCLC) |
| Reason for procedure | Initial assessment |
| Specialty | Combination therapy |
| Therapeutic indication of the resolution |
|---|
|
Lazcluze is indicated in combination with amivantamab for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations |
| Subpopulation | Indication | Comparator |
|---|---|---|
| Adults with advanced NSCLC and EGFR exon 19 deletions or exon 21 L858R substitution mutations; first-line treatment | Afatinib (only for patients with the activating EGFR mutation deletion in exon 19) or osimertinib |
Studies and Results
|
No. of studies
(best subpopulation) |
1 (MARIPOSA) |
|---|---|
|
Study design
(best subpopulation) |
H2H vs. ACT |
|
Meta analysis
(best subpopulation) |
no |
- Clinical trials
- The MARIPOSA trial is an ongoing, multicentre, partially blinded, randomised, controlled, three-arm Phase III trial comparing amivantamab plus lazertinib (Arm A) with osimertinib (Arm B) and lazertinib (Arm C) as monotherapy.
Adults with advanced NSCLC and EGFR exon 19 deletions or exon 21 L858R substitution mutations; first-line treatment
- mortality
- In the MARIPOSA trial, overall survival was defined as the time from randomisation to death from any cause.
- For the overall survival endpoint, the overall population showed a statistically significant survival benefit in favour of lazertinib in combination with amivantamab compared with osimertinib, the extent of which is assessed as a marked improvement.
- An effect modification was observed for the characteristic ‘age’. In the subgroup analysis, a statistically significant advantage in favour of lazertinib in combination with amivantamab was observed for individuals aged < 65 years. In contrast, no statistically significant difference was observed for individuals aged 65 years or older. These subgroup results are considered a relevant finding of the present benefit assessment. They indicate that older patients benefit less from the treatment. However, they are not considered sufficient to allow separate conclusions regarding additional benefit to be drawn in the overall assessment. Furthermore, this effect modification is not observed for other patient-relevant endpoints.
- Morbidity – Symptoms (EORTC QLQ-C30)
- Symptoms of the disease were assessed in the MARIPOSA study using the EORTC QLQ-C30 questionnaire. The analysis of event rates presented in the dossier was not suitable for the benefit assessment. The pharmaceutical manufacturer submitted event time analyses for confirmed deterioration with its response; these form the basis of the present assessment.
- For the endpoints of diarrhoea and loss of appetite, there are statistically significant advantages in favour of lazertinib in combination with amivantamab.
- No differences were observed for the other symptoms: fatigue, nausea and vomiting, pain, dyspnoea, constipation and insomnia.
- Health-related quality of life (EORTC QLQ-C30)
- Disease-related symptoms were assessed in the MARIPOSA study using the EORTC QLQ-C30 questionnaire. The analysis of event rates presented in the dossier was not suitable for the benefit assessment. The pharmaceutical manufacturer submitted event time analyses for confirmed deterioration with its submission, which form the basis of this assessment.
- For the endpoints of physical functioning and role functioning, a statistically significant difference was observed in each case to the disadvantage of lazertinib in combination with amivantamab.
- No differences were observed for the endpoints of global health status, emotional functioning, cognitive functioning and social functioning.
- For the endpoints of physical functioning and role functioning, the overall picture indicates disadvantages. With regard to health-related quality of life, a disadvantage is therefore inferred for lazertinib in combination with amivantamab.
- Side effects – Total adverse events (AEs)
- In the MARIPOSA study, an AE occurred in almost all patients in both the control and intervention arms. The results are presented here for supplementary information only.
- Overall assessment
- Results from the MARIPOSA study are available for the assessment of the additional benefit of lazertinib in combination with amivantamab as first-line treatment for adult patients with advanced non-small cell lung cancer with EGFR exon 19 deletions or exon-21-L858R substitution mutations, results on mortality, morbidity, health-related quality of life and side effects are available from the MARIPOSA study. In this RCT, lazertinib in combination with amivantamab was compared with osimertinib.
- The results for the overall survival endpoint show a statistically significant difference, with a clear advantage for lazertinib in combination with amivantamab. An effect modification by the characteristic ‘age’ is evident. In the subgroup analysis, a statistically significant advantage in favour of lazertinib in combination with amivantamab was observed for individuals aged < 65 years. In contrast, no statistically significant advantage was observed for individuals aged ≥ 65 years. These subgroup results are considered a relevant finding in the present benefit assessment. They indicate that older patients benefit less from the treatment. However, they are not considered sufficient to allow separate conclusions regarding additional benefit to be drawn in the overall assessment. Furthermore, this effect modification is not observed for other patient-relevant endpoints.
- In the morbidity endpoint category, symptoms (EORTC QLQ-C30, NSCLC-SAQ, PGIS) and health status (EORTC QLQ-C30, EQ-5D VAS) were assessed, with positive effects observed for the endpoints of diarrhoea and loss of appetite. Overall, an advantage is inferred for lazertinib in combination with amivantamab.
- With regard to health-related quality of life (EORTC QLQ-C30), an overall disadvantage can be identified due to negative effects on the endpoints of physical functioning and role functioning.
- With regard to side effects, disadvantages for lazertinib in combination with amivantamab are observed for the endpoints SAE, severe AE and therapy discontinuations due to AE, as well as, in detail, for the specific AE ‘venous thromboembolic event’ and other specific UEs. Overall, significant disadvantages can therefore be identified in the side effect category.
- In the overall assessment of the available results for patient-relevant endpoints, the clear advantage in overall survival is offset by significant disadvantages in terms of side effects. Further advantages are evident in the morbidity endpoint category, whilst further disadvantages are observed in health-related quality of life. In a balanced assessment, the G-BA concludes that there is a minor additional benefit for lazertinib in combination with amivantamab as first-line treatment for adult patients with advanced non-small cell lung cancer with EGFR exon-19 deletions or exon-21 L858R substitution mutations.
Courtesy translation only, please refer to the German original.
Associated procedures
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