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G. Naka
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-005 - Overall Survival Results from a Prospective, Multicenter Phase II Trial of Low-Dose Erlotinib as Maintenance in NSCLC Harboring EGFR Mutation (ID 7430)
09:30 - 09:30 | Author(s): G. Naka
- Abstract
Background:
Maintenance therapy with full-dose erlotinib for patients with advanced non-small cell lung cancer (NSCLC) has demonstrated a significant overall survival (OS) benefit. However, 150 mg/day of erlotinib seems too toxic as maintenance therapy. This study aimed to evaluate the efficacy and safety of low-dose erlotinib (25 mg/day) as maintenance treatment after platinum doublet chemotherapy in NSCLC harboring epidermal growth factor receptor (EGFR) mutation.
Method:
Activated EGFR-mutation-positive NSCLC patients who did not progress after first-line platinum-doublet chemotherapy, ≥20 and ≤85 years old, with performance status (PS) 0–3 were included in this study. Low-dose erlotinib (25 mg/day) was administered until disease progression. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), OS, and safety. The required sample size was 40 patients.
Result:
The study was stopped early, after achieving only 28% of planned enrollment, due to poor accrual. Between April 2011 and May 2014, 11 patients (male/female, 5/6; median age, 72 years; PS 0/1, 8/3; stage IV/relapse after surgery, 9/2; exon 19 deletions/L858R, 7/4) were enrolled and accessible in this study. Partial response (PR) was observed in 6 patients (56%). Median PFS was 14.9 months [95% confidence interval (CI), 2.7–27.1 months] and median OS was 40.6 months [95% CI, 24.7-56.5 months] (Figure 1). Toxicities were generally mild. Only one patient developed grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation. Eight patients developed grade 1 skin rash. No treatment-related deaths were observed. Ten patients progressed, and recurrences included brain metastases (n=3), pulmonary metastasis (n=3), local recurrence (n=2), local recurrence plus brain metastasis (n=1), and bone metastasis (n=1). Figure 1
Conclusion:
The study was stopped early due to poor accrual. However, our study suggests that maintenance therapy with low-dose erlotinib might be useful and tolerable in selected NSCLC patients harboring EGFR mutation.
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P2.03-033 - Propensity Score-Adjusted Survival Analysis of Non-Small Cell Lung Cancer Patients with Acquired Resistance to EGFR-TKI (ID 9257)
09:30 - 09:30 | Author(s): G. Naka
- Abstract
Background:
Non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations are treated with EGFR-tyrosine kinase inhibitors (TKIs). However, most patients acquire resistance to EGFR-TKIs and receive subsequent treatments. To determine the optimal treatment for patients with TKI-resistance, we retrospectively examined the outcomes in advanced or recurrent NSCLC patients and analyzed the efficacy of the prevalent treatment options for those with TKI-resistance, using propensity score modeling.
Method:
EGFR-mutated NSCLC patients who acquired resistance to EGFR-TKIs during their first-line EGFR-TKI therapy were assigned to the TKI-resistant group based on the response of progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors. Patients with wild-type (WT) EGFR were assigned to the EGFR-WT group. By multivariate analysis of the two groups, a propensity score for chemotherapy use was calculated for each patient using logistic regression model. TKI treatment-free survival (TFS) was defined as "the overall survival (OS) - total progression-free survival (PFS) of every EGFR-TKI therapy".
Result:
A total of 415 patients with NSCLC were screened for EGFR mutations in the National Center for Global Health and Medicine, from April 2007 through March 2012. Of these, 158 (39%) patients harbored EGFR mutations, and 101 of these patients with activating EGFR mutations developed TKI-resistance. Seventy-five patients with EGFR-mutations who acquired TKI-resistance received a second-line chemotherapy or other EGFR-TKIs. Fifty-seven patients (75%) in the TKI-resistant group received ≥2 lines of EGFR-TKI treatments (beyond PD). Of the 252 EGFR-WT patients, 139 patients who received first-line chemotherapy or EGFR-TKIs formed the EGFR-WT group. OS was significantly longer in the TKI-resistant group compared to the EGFR-WT group (median, 43.8 vs 14.8 months, p<0.001). TFS did not significantly differ between the two groups (median, 16.6 vs 14.4 months, p=0.83). TKI-resistant patients receiving three or two lines of EGFR-TKIs had a better total PFS than those receiving a single line of EGFR-TKI (median, 28.2 vs 21.1 vs 9.0 month, p<0.001). In the propensity score-adjusted multivariate analysis, TFS was significantly associated with the post-operative recurrence (hazard ratio [HR] 0.40, p<0.000) and the use of chemotherapy (HR 0.32, p=0.005). Total PFS of EGFR-TKIs significantly correlated with the post-operative recurrence (HR 0.27, p=0.02) and sequential use of other EGFR-TKIs (HR 0.25, p=0.03).
Conclusion:
The use of chemotherapy prolonged the TFS in TKI-resistant NSCLC patients to the same extent as that seen in EGFR-WT patients. In TKI-resistant patients with EGFR mutations, sequential use of different EGFR-TKIs improved the total PFS of EGFR-TKIs.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-055 - The Usefulness of Liquid Biopsy for ctDNA in Patients with EGFR-Mutant NSCLC During and After Treatment with EGFR-TKIs (ID 9811)
09:30 - 09:30 | Author(s): G. Naka
- Abstract
Background:
Non-small-cell lung cancer (NSCLC) patients with activating mutation of epidermal growth factor receptor (EGFR) gene inevitably develop disease progression to EGFR-tyrosine kinase inhibitors (TKIs). T790M gatekeeper mutation accounts for approximately 60% of the acquired resistance, and osimertinib, third generation EGFR-TKI, is effective against such tumors. Demonstration of T790M requires second biopsy, which is inconvenient and sometimes hazardous. Liquid biopsy of circulating tumor DNA (ctDNA) in the plasma is a non-invasive alternative, but clinical relevance of this method is yet to be fully elucidated.
Method:
NSCLC patients with EGFR mutation undergoing 1st- or 2nd-generation EGFR-TKI treatment are monthly or bi-monthly monitored for plasma ctDNA EGFR mutations, including T790M, by Cobas EGFR mutation test® via 10 ml blood sampling. The treatment could be changed on the attending physicians’ discretion, including osimertinib in patients with documented T790M mutation, with continuation of the monitoring. The primary endpoints are T790M positivity rate of ctDNA among patients with tissue-confirmed T790M mutation, and T790M positivity rate of ctDNA at landmark points, such as radiological progression, clinical deterioration or second biopsy of the tumor. The secondary endpoints include EGFR mutation detection rate of plasma ctDNA at landmark points, the interval of tissue and plasma T790M detections, and response rate and progression-free survival in patients treated with osimertinib according to plasma/tissue T790M status.
Result:
From Oct 2016 to Mar 2017, 121 eligible patients were enrolled. The median age 73 years (range, 42-92), 42 male (34.7%), PS 0, 1 and 2 were 64 (52.9%), 54 (44.6%) and 3 (2.5%) respectively. EGFR mutation types were 61 patients (50.4%) del 19, 55 (45.5%) L858R and 5 (4.0%) others. 80 (66.1%) were never smokers. At the time of EGFR-TKI initiation, 82 (67.8%) had advanced and 39 (32.2%) had recurrent diseases. 65 (53.7%) had any prior therapy, including 21 (14.8%) with prior cytotoxic chemotherapy. Used EGFR-TKIs were gefitinib 50 (41.3%), erlotinib 40 (33.1%), and afatinib 31 (25.6%). Newly-diagnosed/on TKI therapy at enrollment was 18 (14.9%)/103 (85.1%). The median follow-up is 12[鈴木1] months. So far, plasma T790M was detected in 8 patients.
Conclusion:
This observational study will elucidate the clinical usefulness and limitations of monitoring of ctDNA for T790M mutation in the real-world setting.
