Abstract 5921
Background
Afatinib (AFA), an irreversible ErbB family blocker, is used at the standard starting dose of 40mg for the treatment of patients with EGFR M+ NSCLC. It has been shown previously tolerability guided dose reduction effectively decreases incidence and severity of treatment related adverse events (AEs) during the treatment, and that treatment-related dose reduction was more likely in patients who had higher plasma concentrations of AFA before dose adaptation (Yang et al., Annals of Oncology 2016). After dose reduction, concentrations were similar to those obtained in patients who did not experience AEs, with comparable efficacy. We thus intended to determine a threshold concentration related with dose-reduction or AEs leading to dose-reduction (AELDR).
Methods
Patients (N = 390) with AFA treatment, analyzable trough plasma concentration (Cmin) determination at D22 and follow-up of at least 6 months were identified from LUX-Lung (LL3 & LL6) studies. Receiver operating characteristic (ROC) curve analysis (univariable regression model) was performed to assess a discrimination potential of AFA Cmin for AELDR.
Results
The most discriminating threshold of AFA Cmin associated with dose reduction or AELDR between D22 sampling and M6 is at 34 ng/ml. With this concentration threshold, there is a maximal AUC of 0.63 (95%CI: [0.58 – 0.69], a maximal Younden index of 0.267 (49% sensitivity, 78% specificity), with an odds ratio of 3.37 [2.10 – 5.40]) indicating that dose reduction or AELDR are more frequent in patients with concentration ≥34 ng/mL. The analysis also showed that concentration is more often elevated in female, older (>65y), eastern Asian and low-body weight patients.
Conclusions
Monitoring of AFA plasma levels might be useful for the management of AEs in patients with NSCLC, especially for patients having factors known to be associated with higher AFA plasma exposure or toxicities. These results support the approach of adapting treatment dose based on plasma concentrations of AFA both forAEs and efficacy.
Clinical trial identification
NCT01121393, NCT00949650.
Editorial acknowledgement
Legal entity responsible for the study
M. Molimard.
Funding
Boehringer Ingelheim.
Disclosure
C. Frohn: Full / Part-time employment: Boehringer Ingelheim International GmbH. C. Maritaz: Full / Part-time employment: Boehringer Ingelheim France. All other authors have declared no conflicts of interest.
Resources from the same session
3683 - Impact of Radiotherapy on efficacy of anti-programmed death 1 (PD-1) antibodies in metastatic NSCLC
Presenter: Evangeline Samuel
Session: Poster Display session 1
Resources:
Abstract
3924 - Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real World Data from a European Cohort with focus on subgroups of interest
Presenter: Giannis Mountzios
Session: Poster Display session 1
Resources:
Abstract
3970 - Patients with metastatic non-small cell lung cancer and PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Martin Sebastian
Session: Poster Display session 1
Resources:
Abstract
5350 - The efficacy and safety of pembrolizumab as a first-line therapy in PD-L1 50% positive advanced NSCLC (HOPE-001)
Presenter: Motohiro Tamiya
Session: Poster Display session 1
Resources:
Abstract
3832 - Osimertinib in epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC): analysis of patients with central nervous system (CNS) metastases in a real-world study (ASTRIS)
Presenter: Giulio Metro
Session: Poster Display session 1
Resources:
Abstract
4082 - Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI)
Presenter: Riyaz Shah
Session: Poster Display session 1
Resources:
Abstract
2855 - Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumor DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global Ph3 study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations
Presenter: Kazuto Nishio
Session: Poster Display session 1
Resources:
Abstract
2911 - Apatinib combined with EGFR - TKI in treating advanced non-small cell lung cancer with EGFR - TKI resistance
Presenter: Ruifen Tian
Session: Poster Display session 1
Resources:
Abstract
2100 - Updated analysis of a phase I trial of afatinib (Afa) and bevacizumab (Bev) in chemo-naïve patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring EGFR-mutations: OLCSG1404
Presenter: Takashi Ninomiya
Session: Poster Display session 1
Resources:
Abstract
4325 - Multiple synchronous mechanisms may contribute to osimertinib resistance in non-small cell lung cancer (NSCLC) patients: insights of the MATCH-R study
Presenter: Diego Enrico
Session: Poster Display session 1
Resources:
Abstract