Overview
FIRST-LINE TAGRISSO® – THE STANDARD FOR THE FIRST-LINE THERAPY OF ADVANCED EGFRm NSCLC1,2#
OS
Longer survival
38,6 months – first and only EGFR TKI with >3 years statistically significant OS3
- vs 31.8 months OS for gefitinib/erlotinib (HR = 0.799; p = 0.0462)
PFS
Later progression
18,9 months – a PFS that has never been achieved before4*
- vs 10.2 months PFS for gefitinib/erlotinib (HR = 0.46; p < 0.0001)
CNS
Less CNS progression
52 % significant reduction in the risk of CNS progression3,5
- vs gefitinib/erlotinib (HR = 0.48; p = 0.014)
- # Based on the ESMO and NCCN Guidelines. Osimertinib (TAGRISSO®) is the only first-line monotherapy option for patients with advanced EGFRm NSCLC preferred by the European Society for Medical Oncology (ESMO) Guidelines Committee and National Comprehensive Cancer Network® (NCCN®).
- * Based on monotherapies in the 1L.
Study design
FIRST-LINE therapy for advanced NSCLC with EGFR mutation4
FIRST-LINE TAGRISSO® was studied in a double-blind, randomised phase III study vs EGFR TKI comparator arm (gefitinib/erlotinib)4
Primary endpoint: PFS determined by the investigator (RECIST v1.1)4
Secondary endpoint: OS, ORR, DoR, DCR, depth of response, safety4
- * Patients with asymptomatic or stable CNS metastases were included; symptomatic/ non-stable CNS metastases were allowed if they were stable for ≥2 weeks after stopping the definitive therapy and taking corticosteroids.4
Tumour assessments were performed at baseline and then every 6 weeks for 18 months. Subsequently, the assessment took place every 12 weeks until disease progression. Brain imaging at baseline was prescribed only for patients with known or suspected brain metastases, with follow-up imaging in patients with confirmed CNS metastases.4 - # 47%: 85/180 patients, who have received a second-line therapy. 31%: 85/277 patients of the EGFR TKI comparator arm.
- OS: Overall survival; ORR: Objective response rate; DoR: Median duration of response; DCR: Disease control rate.
Results
- OS
- PFS
- CNS progression
- Patients under therapy
FIRST-LINE TAGRISSO® provides a statistically significant benefit over sequential therapy with TAGRISSO® 2L3
STATISTICALLY SIGNIFICANT OVERALL SURVIVAL (OS)
Despite 47% Crossover, significantly longer survival with FIRST-LINE TAGRISSO®3
- Adapted according to Ramalingam et al. 2019.3
- # 47%: 85/180 patients, who have received a second-line therapy. 31%: 85/277 patients of the EGFR TKI comparator arm.
Safety
Preferable tolerability profile of TAGRISSO® despite almost double the exposure time3
- *Grouped term.
- **Listed are adverse events that occurred in at least 10% of patients in both study arms. The safety analyses included all patients who had received at least one dose of an investigational preparation (safety analysis set). Some patients had more than one adverse event. In the osimertinib group, the only adverse events were 4th grade stomatitis and renal symptoms (1 patient each); the only 5th grade adverse event was renal symptoms (1 patient). In the comparator arm, the only grade 4 adverse event was an elevation in alanine aminotransferase level (4 patients); the only grade 5 undesirable event was diarrhoea (1 patient). In the comparator arm, 1 patient had diarrhoea of unknown grade and 1 patient had nausea of unknown grade. #The most frequent undesirable events in the kidneys in both experimental groups were an increase in creatinine levels in the blood, one acute renal damage, one proteinuria, dysuria and haematuria.
- ADR: adverse drug reaction; fewer ADR grade ≥3 for osimertinib 42% vs 47% in comparator arm; ALT: alanine aminotransferase; AST: aspartate aminotransferase; EKG: electrocardiogram.
References:
- Planchard D, et al; on behalf of the ESMO Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Originally published in 2018 – Ann Oncol. 2018:29(Suppl 4):iv192–iv237.Updated version published 15 September 2020 by the ESMO Guidelines Committee, https://www.esmo.org/guidelines/lung-and-chest-tumours/clinical-practice-living-guidelines-metastatic-non-small-cell-lung-cancer.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.9.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 30, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
- Ramalingam SS, et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC; N Engl J Med. 2020; 382:41-50.
- Soria JC, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer; N Engl J Med 2018; 378(2) inkl. Appendix: 113–125.
- Reungwetwattana T, et al. CNS Response to Osimertinib Versus Standard Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 36:3290-3297.
Professionals can request the mentioned references from AstraZeneca AG.
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