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X. Wang
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ORAL 17 - EGFR Mutant Lung Cancer (ID 116)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:P. Meldgaard, E. Felip
- Coordinates: 9/08/2015, 10:45 - 12:15, Four Seasons Ballroom F3+F4
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ORAL17.02 - Randomized Trial of Gefitinib with and without Pemetrexed as First-Line Therapy in East-Asian Patients with Advanced NS NSCLC with EGFR Mutations (ID 1319)
10:56 - 11:07 | Author(s): X. Wang
- Abstract
- Presentation
Background:
Pemetrexed (P) is the standard of care for non-squamous non-small cell lung cancer (NS NSCLC), whereas epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib (G), are the standard of care for advanced NSCLC with EGFR mutations. Clinical and nonclinical studies have demonstrated synergistic effects of EGFR TKIs and P. Based on these observations, the efficacy and safety of G+P was compared with G monotherapy in patients with NS NSCLC positive for activating EGFR mutations.
Methods:
The primary objective of this randomized, multicenter, open-label, parallel-arm, phase 2 East-Asian study was to assess whether G+P prolongs progression-free survival (PFS) versus G alone. Secondary endpoints included overall survival (OS), overall response rate, disease control rate, time to progressive disease, duration of response, and treatment-emergent adverse events (TEAEs). Eligible patients had stage IV NS NSCLC with activating EGFR mutations, were chemonaïve, and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Patients were randomized in a 2:1 ratio (G+P:G). Dosing schedule was concurrent G (250 mg/day) and P (500 mg/m[2] every 3 weeks) in the G+P arm and G monotherapy (250 mg/day) in the G arm. Treatment continued until progression or unacceptable toxicity. The primary endpoint was analyzed after 144 events, which provided 70% power at a 1-sided 20% significance level, assuming a true hazard ratio (HR) of 0.79.
Results:
Between February 2012 and August 2013, 191 patients were randomized and treated (G+P: N=126; G: N=65). Patients were mostly female (64.4%) with a mean age of 62 years; most were never-smokers (67.0%), had confirmed stage IV disease (84.8%), and ECOG PS of 1 (68.6%). Overall, 55.0% had exon 19 deletions, 39.3% had exon 21 L858R mutations, and 5.8% had other activating EGFR mutations. Baseline characteristics were balanced between treatment arms. Patients in the G+P arm received 96.3% and 92.9% of the planned mean dose of G and P, respectively; patients in the G arm received 97.9% of the planned mean dose of G. Median PFS for G+P (15.8 months) was significantly longer than for G (10.9 months); HR=0.68; 95% confidence interval 0.48, 0.96; 1-sided P=0.014; 2-sided P=0.029. OS data are immature and will be reported at study completion. The incidence of grade 3/4 study drug-related TEAEs was significantly higher for G+P (42.1%) than for G (18.5%); P=0.001. The most common study drug-related TEAEs for G+P were diarrhea (44.4%), aspartate aminotransferase increased (41.3%), and dermatitis acneiform and alanine aminotransferase increased (38.1% for each), and for G were diarrhea (47.7%), dermatitis acneiform (43.1%), and dry skin (35.4%). The proportion of treatment discontinuations due to TEAEs was 16.7% in the G+P arm and 9.2% in the G arm; 2 patients (G+P arm) died due to study drug-related adverse events.
Conclusion:
The combination of G+P led to a significant improvement in PFS compared with G monotherapy for East-Asian patients with EGFR mutation-positive NS NSCLC, and met the primary study endpoint. The incidence of grade 3/4 study drug-related AEs was higher for G+P than for G. ClinicalTrials.gov identifier: NCT01469000.
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-063 - Dynamic Change of Fatigue for East-Asian Patients in the JMEN Trial (ID 843)
09:30 - 09:30 | Author(s): X. Wang
- Abstract
Background:
In the JMEN trial (Ciuleanu et al., Lancet 374:1432-1440, 2009), patients with advanced non-squamous non-small cell lung cancer (NSCLC) derived a benefit from pemetrexed maintenance therapy after platinum-based initial therapy by extending survival, delaying disease progression, and maintaining overall quality of life (QoL). However, fatigue was the most common physician-reported toxic effect in the pemetrexed treated group. We conducted a post-hoc analysis to investigate the dynamic change of fatigue in overall population and East-Asian (EA) patients treated on the JMEN trial.
Methods:
This analysis was performed in the overall safety population (N=656) and the EA subgroup safety population (N=152) mainly from China, Taiwan, and Korea including squamous and non-squamous NSCLC patients. The Common Terminology Criteria for Adverse Events (version 3.0) was used for summary of the AE incidence rates by cycle and AE severity reported by investigator. The Lung Cancer Symptom Scale (LCSS) was used to evaluate patients’ QoL. Worsening of fatigue was defined as an increase of 15 mm or more from baseline on a 100 mm scale in LCSS reported by the patients. The percentage of patients with worsening fatigue was also summarized by cycle. The time to worsening of fatigue symptom was analyzed using Kaplan-Meier method and Cox proportional model.
Results:
In the EA population drug-related fatigue (grade 1-4) occurred more frequently in pemetrexed arm compared with placebo arm (30.4% vs 16.0%, p=0.075). The grade 3/4 drug-related fatigue was rare in both arms (1 event reported in each arm). For both overall and EA populations, the fatigue incidence by cycle during the maintenance treatment with pemetrexed did not increase during subsequent cycles (Figure 1A, B). The percentage of patients who experienced worsening of fatigue based on the patients-reported LCSS scores was also comparable between the two arms in the overall and EA populations (Figure 1C, D). EA Patients in the pemetrexed arm experienced a numerically longer median time to worsening of fatigue compared to EA patients in the placebo arm, although the difference is not statistically significant (5.95 months vs. 3.91 months, HR= 0.84, 95% confidence interval [CI]: 0.51-1.37, p= 0.471). Figure 1
Conclusion:
These analyses suggest that despite a higher incidence of grade 1/2 drug-related fatigue compared with placebo, pemetrexed maintenance treatment for EA patients with advanced NSCLC will not impair patient-reported QoL.