Virtual Library
Start Your Search
Akihiko Gemma
Author of
-
+
P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 3
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.14-41 - Risk Factors for Brain Metastasis in Patients with EGFR Mutant Non-Small Cell Lung Cancer (ID 1036)
10:15 - 18:15 | Author(s): Akihiko Gemma
- Abstract
Background
Brain metastasis is associated with a poor prognosis in patients with EGFR mutant non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) may be an effective treatment, but their influence on brain metastasis development is unclear. We aimed to identify risk factors for brain metastasis in patients with EGFR-mutant NSCLC.
Method
This retrospective study included 166 consecutive advanced NSCLC patients with EGFR major mutations (Ex 21 L858R or Ex 19 del) who received EGFR–TKI monotherapy at the Nippon Medical School Hospital and Nippon Medical School Tamanagayama Hospital from November 2010 to June 2018. Patients who had brain metastases before EGFR–TKI monotherapy were excluded. We evaluated the cumulative actuarial incidence of brain metastases by Gray’s test, univariate and multivariate analyses.
Result
The median age was 72 years (range, 26-95 years), the majority of patients were female (n=103), and most patients had adenocarcinoma (n=153). Patients carried either an EGFR L858R (n=88) or 19del (n=78) mutation, and had been treated with gefitinib (n=97), erlotinib (n=22) or afatinib (n=47). The time to brain metastasis did not significantly differ between the three EGFR-TKI groups. The time to brain metastasis was significantly shorter in patients <75 years than >75 years (29.0 months versus not reached; HR 4.70; 95% CI 1.72-12.87). Univariate and multivariate analyses showed that age <75 years and non-adenocarcinoma histology were significant predictors of brain metastasis. In patients <75 years, the time to brain metastasis in patients who underwent EGFR-TKI dose reduction or intermittent treatment was significantly shorter than patients with constant EGFR-TKI treatment (24.9 versus 39.9 months; HR 2.40; 95% CI 1.10-5.22).
Conclusion
Age <75 years is a risk factor for brain metastasis in patients with EGFR mutant NSCLC. We do not recommend EGFR–TKI dose reduction or intermittent administration in these patients.
-
+
P2.14-52 - The Results from Plasma EGFR Mutation Analysis in NEJ026 Study (ID 602)
10:15 - 18:15 | Author(s): Akihiko Gemma
- Abstract
Background
EGFR mutation analysis of plasma circulating tumor DNA (ctDNA) has been reported to be useful to detect resistant mutations and to predict the efficacy of treatment. In NEJ026 study, we demonstrated the PFS of erlotinib plus bevacizumab (BE) treatment was significantly superior to the erlotinib alone (E) in NSCLC patients harboring EGFR mutation. Evaluation of plasma EGFR mutations included in NEJ026 study as preplanned analysis.
Method
At the time points of pretreated (P0), 6 weeks after study treatment started (P1), and confirmed progressive disease (P2), the plasma samples were collected from the patients enrolled to NEJ026 study. The number of enrolled patients were 112 in BE and 114 in E. Plasma ctDNA analysis for detection of the activating EGFR mutation and T790M mutation were performed by modified PNA-LNA PCR clamp method.
Result
The total numbers of collected plasma samples in BE and E were 108 (96.4%) and 107 (95.5%) at P0, 95 (84.8%) and 97 (86.6%) at P1, and 42 (37.5%) and 53 (47.3%) at P2, respectively. In eligible patients having EGFR activating mutation detected by cytohistological specimens, detection rate of plasma EGFR mutation at P0 was 68% (147/215). The detection ratio of T790M mutation at P2 were similar in both arms: 8 (19.0%) in BE and 11 (20.8%) in E. By detection pattern of activating EGFR mutation, PFS was evaluated among three groups: type A (P0 (-),P1 (-)), type B (P0 (+), P1(-)), and type C (P0 (+), P1(+)). Type A achieved the best response to both TKI [Type A BE: 18.1 M (n = 32, 95% CI, 11.5 to upper limit not reached(NR)), E: 16.7 M (n = 26, 95% CI, 11.2 to NR )]. Type B also had better PFS to TKI and BE is more favorable effect than E compared to other types [type B BE: 15.5 M (n = 48, 95% CI, 12.4 to 23.3), E: 11.1 M (n = 57, 95% CI, 8.5 to 13.7)]. Type C showed worse response to both treatment [type C BE: 6.0M. (n = 12, 95% CI 2.6 to NR), E: 4.3 M (n = 10, 95% CI, 2.8 to 20.2)]. BE had better PFS in all types.
Conclusion
Frequency of T790M in P2 was similar among BE and E. When patients still had detectable activating EGFR mutation in plasma ctDNA after treatment for 6 weeks, you should consider that they might have poor response to both BE and E.
-
+
P2.14-55 - Real-World Safety and Efficacy Data of Osimertinib in Patients from Japan with EGFR T790M-Positive NSCLC (ID 1601)
10:15 - 18:15 | Author(s): Akihiko Gemma
- Abstract
Background
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was approved in Japan on 28 March 2016 as second- or later-line treatment for patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) who have progressed on EGFR-TKIs. Post-marketing activities included the Japan-local All-patient Clinical Experience Investigation, reporting Japanese real-world safety and efficacy of osimertinib in the approved indication.
Method
Overall, 3629 patients investigated at 718 hospitals between 28 March 2016 and 31 August 2018 were included. Adverse events were assessed by attending physicians to determine whether they were possibly causally-related to osimertinib. Osimertinib antitumour activity was evaluated by attending physicians using RECIST version 1.1. Progression-free survival (PFS) and overall survival (OS) were also analysed. The planned observation period was 12 months.
Result
The median observation period for patients in the safety analysis set (n=3578) was 343 days (range: 1–764). Adverse drug reactions occurred in 58.1% (2079/3578) of patients. Adverse drug reactions (as per Japanese Prescribing Information) of interstitial lung disease, prolonged QT interval, liver disorder, and haematotoxicity were reported in 6.8% (245/3578) (Gr≥3, 2.9% [104/3578]), 1.3% (45/3578) (Gr≥3, 0.1% [5/3578]), 5.9% (212/3578) (Gr≥3, 1.0% [35/3578]), and 11.4% (409/3578) (Gr≥3, 2.9% [104/3578]) of patients, respectively. The objective response rate and disease control rates for patients in the efficacy analysis set (n=3563) were 69.9% (2492/3563; 95% confidence interval [CI] 68.4, 71.4) and 86.7% (3090/3563; 95% CI 85.6, 87.8). PFS rates at 6 months and 12 months were 77.4% (95% CI 75.9, 78.9) and 53.2% (95% CI 51.3, 55.1). OS rates at 6 months and 12 months were 88.3% (95% CI 87.2, 89.4) and 75.4% (95% CI 73.8, 77.0). Selected subgroup analyses of efficacy are presented in Table 1.
Conclusion
These data support the currently established benefit–risk assessment of osimertinib in patients with EGFR T790M positive NSCLC.
