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A. Chougule
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 5
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-007 - Differential Efficacy of Gefitinib in Exon 19 or Exon 21 Mutated Adenocarcinoma Lung (ID 5667)
14:30 - 14:30 | Author(s): A. Chougule
- Abstract
Background:
This study has been designed to evaluate the differential effect of EGFR mutation status (exon 19 versus 21) on PFS and OS in treatment naïve advanced EGFR Mutation positive adenocarcinoma lung treated with Gefitinib as first line agent
Methods:
This was a post hoc analysis of EGFR mutated (exon 19 and 21) advanced-stage (Stage IIIB or IV), chemotherapy-naive NSCLC patients treated with gefitinib as first line in a phase 3 randomized study. Patients were treated with Gefitinib 250 mg daily. Patients underwent axial imaging for response assessment on D42, D84, D126 and subsequently every 2 months till progression. Responding or stable patients were treated until progression or unacceptable toxicity. SPSS was used for statistical analysis. Kaplan Meier method was used for survival estimation and log rank test for comparison. Cox proportion hazard model was used for multivariate analysis.
Results:
141 patients were eligible for analysis of which 78 were males and 63 were females. 127 patients (90.1%) were ECOG 0-1 while 14 patients (9.1%) were ECOG >1. Exon 21 mutation was present in 65 patients (46.1%) and exon 19 mutation in 76 patients (53.9%). 133 of 141 patients were evaluable for response. Response rate of patients having exon 19 mutation was 72.9% (51 patients, n=70) while it was 55.6% in patients having exon 21 mutation (35 patients, n=63) {p=0.046}. Median PFS in exon 19 mutated patients was 9.3 months (95% CI 6.832-11.768) compared to 7.8 months (95% CI 5.543-10.047) in exon 21 mutated patients (p=0.699). The median OS in exon 19 mutated patients was 19.8 months (95 % CI 16.8-22.7) and 16.5 months (95% CI 10.9-22.1) in exon 21 mutated patients (p=0.215).Only female gender had a positive impact on both PFS and OS on multivariate analysis.
Results:
141 patients were eligible for analysis of which 78 were males and 63 were females. 127 patients (90.1%) were ECOG 0-1 while 14 patients (9.1%) were ECOG >1. Exon 21 mutation was present in 65 patients (46.1%) and exon 19 mutation in 76 patients (53.9%). 133 of 141 patients were evaluable for response. Response rate of patients having exon 19 mutation was 72.9% (51 patients, n=70) while it was 55.6% in patients having exon 21 mutation (35 patients, n=63) {p=0.046}. Median PFS in exon 19 mutated patients was 9.3 months (95% CI 6.832-11.768) compared to 7.8 months (95% CI 5.543-10.047) in exon 21 mutated patients (p=0.699). The median OS in exon 19 mutated patients was 19.8 months (95 % CI 16.8-22.7) and 16.5 months (95% CI 10.9-22.1) in exon 21 mutated patients (p=0.215).Only female gender had a positive impact on both PFS and OS on multivariate analysis.
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P3.02b-055 - Impact of Pemetrexed Chemotherapy in Exon 19 or Exon 21 Mutated NSCLC (ID 5968)
14:30 - 14:30 | Author(s): A. Chougule
- Abstract
Background:
EGFR mutation subtype is being increasingly recognized as factor impacting outcome of patients receiving oral TKI in non-small cell lung cancer. Data for the effect of this factor on the outcome in patients receiving chemotherapy is limited. We have the post hoc analysis of the study at our center to answer this question..
Methods:
We completed a study comparing pemetrexed with platinum vs. oral TKI in EGFR mutation positive patients in lung cancer. We analyzed the impact of EGFR mutation subtype, exon 19 and 21 on the PFS and OS of patients treated with pemetrexed (500mg/m2 on day 1) and carboplatin (AUC 5 on day 1) as first line therapy every 21 days. Patients underwent axial imaging for response assessment on D42, D84, D126 and subsequently every 2 months till progression. Responding or stable patients were treated until progression or unacceptable toxicity (post 6 cycles, patients were offered maintenance pemetrexed every 21 days).
Results:
143 patients received pemetrexed based therapy as first line treatment for stage III/IV NSCLC in the chemotherapy arm. 51 patients (36%) had exon 21 mutation while 92 patients (64%) had exon 19 mutation. Response rates in evaluable patients was 47.7% in exon 19 patients (41 patients, n=86) and 42.9 % in exon 21 patients (18 patients , n=42).There was a differential impact of EGFR mutation on PFS (p=0.028, HR=1.787 , 95% CI 1.066- 2.998) in favour of exon 19 mutation. They also had a significant increase in median overall survival (24.5 months, 95% CI 21.3-27.7 months ) over the exon 21 mutated patients (18.1 months,95% Cl 13.5-22.6 months, p=0.002).
Conclusion:
In this study, EGFR exon 19 mutation had a differential impact on both PFS and OS in Indian patients of advanced-stage NSCLC treated with chemotherapy.
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P3.02b-058 - Second-Line Therapy in EGFR Activating Mutation Positive Advanced NSCLC: Analysis from a Randomized Phase III First-Line Trial (ID 5591)
14:30 - 14:30 | Author(s): A. Chougule
- Abstract
Background:
To evaluate the efficacy of second line therapy in patients progressing on either a Pemetrexed-Platinum doublet or Gefitinib in an epidermal growth factor receptor (EGFR) activating mutation positive Stage IIIB/IV non small cohort in the setting of a phase III clinical trial evaluating Pemetrexed-Platinum doublet versus Gefitinib as first line therapy
Methods:
Patients were part of a randomized Phase III open label parallel group study comparing Gefitinib with Pemetrexed- Platinum doublet in the upfront setting in an EGFR mutation positive Stage IIIB/IV lung cancer population. On progression on first-line therapy, patients were started on second line therapy, if Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0-2 and baseline clinical and biochemical parameters were within acceptable limits. Patients who received Pemetrexed-Platinum in the first line were offered Gefitinib in the second-line while patients progressing on first-line Gefitinib were considered for Pemetrexed-Platinum doublet as second-line therapy.
Results:
187 patients were included for analysis.Out of these 157 patients were evaluable for response. 113 patients had received gefitinib as second line ,while 74 patients had received other I.V second line chemotherapy. The response rate was 60.6% in Gefitinib cohort (60, n=99) and 31% in non -Gefitinib cohort (18, n=58), {p=0.30}. The median PFS was 7.4 months (95% CI:5.4-9.4) in gefitinib cohort, whereas it was 4.4 months in non -gefitinib cohort (95% CI:3.7 -5.2). Median OS in gefitinib cohort was 14 months (95% CI:10.8-17.2), while it was 9.8 months in non -gefitinib cohort (95% CI:7.8-11.7){p-0.007}
Conclusion:
Patients started on gefitinib post progression on pemetrexed therapy had significant benefit, whereas it was limited in patients who received I.V chemotherapy post Gefitinib.
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P3.02b-065 - Third Line Therapy in EGFR Positive Advanced Non-Small Cell Lung Cancer (ID 5629)
14:30 - 14:30 | Author(s): A. Chougule
- Abstract
Background:
This study was designed to evaluate the response and outcomes to third line chemotherapy in classic activating EGFR mutation positive non small cell lung cancer (NSCLC) who had progressed on both TKI and intravenous chemotherapy
Methods:
85 EGFR mutation positive NSCLC patients who had received both TKI and intravenous chemotherapy(mainly Pemetrexed and platinum, 80 patients) were selected for this analysis. The treatment regimens, response in accordance with RECIST v1.1 and treatment outcomes were noted. Descriptive statistics was performed. Kaplan Meier survival analysis was used for estimation of PFS and OS.
Results:
85 patients received third line therapy of which weekly paclitaxel was given in 43(50.6%) patients, Docetaxel in 15(17.6%) patients, Gemcitabine in 6(7.1%) patients , rechallenged TKI in 11(13%) patients and other chemotherapy in 10(11.8%)patients. Out of 85 patients , 67 were evaluable for response; 13(19.4%) patients had partial response, 34(50.7%) patients had stable disease and 20(29.9%)patients had progression as best response. In 7 patients chemotherapy had to be stopped. It was because of toxicity in 5 patients and patients preference in 2 patients. The median PFS & OS were 4.2 months (95% CI 3.4-4.9 months) and 8.4 months (95% CI 6.9-9.9 months) respectively. There was no difference in PFS and OS between weekly Paclitaxel and other regimens.
Conclusion:
Third line therapy in EGFR mutated patients post TKI and Pemetrexed progression is associated with meaningful PFS and OS.
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P3.02b-090 - Pemetrexed versus Gefitinib in EGFR Mutation Positive Lung Cancer: Results of a Phase 3 Study from India (ID 5416)
14:30 - 14:30 | Author(s): A. Chougule
- Abstract
Background:
This study has been designed to confirm the efficacy of gefitinib Platinum and Pemetrexed combination chemotherapy as first-line treatment for advanced EGFR Mutation positive adenocarcinoma lung.
Methods:
This was an open label, randomised, parallel group study comparing Gefitinib ( 250 mg OD daily) with Platinum ( either Cisplatin 75 mg/m2 or Carboplatin AUC-5 ) and Pemetrexed ( 500 mg/m2 ) doublet intravenous chemotherapy regimen ( Induction of 4-6 cycles followed by maintenance) in patients with stage IIIB or stage IV adenocarcinoma lung who have confirmed to be EGFR activating mutation-positive in the first line setting. The primary endpoint for the study is progression free survival (PFS). Patients underwent axial imaging for response assessment on D42, D84, D126 and subsequently every 2 months till progression. Patients were followed up till death. For an estimated 50% improvement in progression free survival, with 80 % power and 5% type one error, number of patients required will be 260. We expect a 5% dropout rate, which required 290 patients to be randomized.
Results:
The median PFS in gefitinib arm was 8.433 months ( 95% CI 6.332-10.535) while it was 5.6 months ( 95% CI 4.207-6.993) in pemetrexed arm ( p value-0.000 , log rank test). The adjusted hazard ratio was 0.661 (95% CI 0.513- 0.852) . The impact of gefitinib on PFS was seen across all subgroups Table 1. There was no statistically significant difference in overall survival between the 2 arms .
Table 1 : Impact of gefitinib on progression free survival in different subgroups.Variable Subgroup HR 95%CI HR P value Age Below 65 years 0.66 0.50-0.86 0.003 Above 65 years 0.35 0.18-0.68 0.002 Gender Male 0.66 0.47-0.92 0.014 Female 0.66 0.45-0.97 0.037 Smoking Smoker 0.60 0.34-1.04 0.071 Non smoker 0.60 0.45-0.79 0.000 Oral tobacco use Yes 0.62 0.41-0.92 0.018 No 0.57 0.41-0.79 0.001 ECOG PS PS0-1 0.62 0.48-0.82 0.001 PS2 0.51 0.23-1.10 0.087 Presence of liver metastasis Yes 0.55 0.33-0.91 0.020 No 0.63 0.48-0.85 0.002 Presence of brain metastasis Yes 0.56 0.30-1.06 0.073 No 0.61 0.46-0.80 0.000
Conclusion:
The study confirms superiority of gefitinib against the the most active chemotherapy regimen of pemetrexed platinum in EGFR mutated NSCLC patients.
