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Akshar Dash
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-10 - Pembrolizumab in Combination with Chemotherapy as First-Line Treatment of Advanced Non-Small Cell Lung Cancer (Now Available) (ID 1151)
08:00 - 18:00 | Author(s): Akshar Dash
- Abstract
Background
Pembrolizumab, a monoclonal antibody directed against programmed death-1 (PD-1), has been established as preferred treatment as a monotherapy for advanced non-small cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) expression of ≥ 50%. Combining immunotherapy with chemotherapy have shown synergistic anticancer activities and pembrolizumab has been studied in combination with various traditional chemotherapy regimens as first-line treatment for advanced NSCLC. Hence, we performed a systematic review and meta-analysis of currently available randomized controlled trials (RCTs) to evaluate the efficacy pembrolizumab in combination with chemotherapy as first-line treatment of advanced NSCLC.
Method
We conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs utilizing first-line pembrolizumab chemoimmunotherapy in patients with advanced NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-test. Random effects model was applied.
Result
3 RCTs (Keynote-021,189 and 407) including 1298 patients with advanced NSCLC were included in the analysis. The study arm used standard chemotherapy regimens in combination with pembrolizumab while control arm used only standard chemotherapy regimens. The randomization ratio was 2:1 in Keynote-189 study and 1:1 in other studies. The I2 statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The pooled HR for PFS was statistically significant at 0.54 (95% CI: 0.47-0.62; P < 0.00001), including in PD-L1 tumor proportion score (TPS) of less than 1% cohort (HR: 0.72; 95% CI: 0.56-0.92; P = 0.010) and PD-L1 TPS ≥ 1% cohort (HR: 0.46; 95% CI: 0.39-0.56; P < 0.00001). The pooled HR for OS was 0.59 (95% CI: 0.45-0.76; P < 0.0001). Improvement in OS was also seen across all PD-L1 categories: in PD-L1 <1% group HR was 0.60 (95% CI: 0.43-0.83; P = 0.002) and in PD-L1 ≥ 1% group HR was 0.55 (95% CI: 0.40-0.75; P = 0.0002).
Conclusion
Our meta-analysis demonstrated that first-line chemoimmunotherapy with pembrolizumab significantly improved PFS and OS compared to standard chemotherapy in patients with advanced NSCLC. The improvement of PFS and OS were consistent across all PD-L1 expression categories.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-78 - Treatment-Related Adverse Events in Patients with Advanced NSCLC Treated with First-Line Atezolizumab Chemoimmunotherapy (Now Available) (ID 1192)
09:45 - 18:00 | Author(s): Akshar Dash
- Abstract
Background
Non-small cell lung cancer (NSCLC) accounts for majority of lung cancer, the leading cause of cancer-related mortality in both sexes. Atezolizumab, an anti- programmed death ligand 1 (PDL-1) antibody, has shown significant antitumor activity against NSCLC. Atezolizumab in combination with chemotherapy as a first-line treatment of advanced NSCLC have shown to improve survival in recent studies. Yet, there are notable adverse events. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of treatment-related adverse events (TRAE) and treatment discontinuation due to TRAE.
Method
We performed a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and various meeting abstracts from inception through March 2019. RCTs utilizing first-line atezolizumab combination regimen in patients with advanced NSCLC were incorporated in the analysis. The primary meta- analytic approach was a random effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-statistic.
Result
4 RCTs (IMpower – 130, 131, 132 and 150) including 2725 patients with advanced NSCLC were included in the meta-analysis. The study arm used standard chemotherapy regimens in combination with atezolizumab while control arm utilized only standard chemotherapy regimens. The randomization ratio was 2:1 in IMpower130 study and 2:1 in other studies. The I2 statistic for heterogeneity was 0, suggesting homogeneity among RCTs. All-grade TRAE incidence was 94.5% in study group vs 91.8% in control group (RR, 1.03; 95% CI: 0.99 – 1.06, P = 0. 01). High-grade TRAE was 12.94% higher in study arm compared to control arm (RR, 1.22; 95% CI: 1.14 – 1.30, P < 0.0001). Treatment-related deaths were reported in 34 (2.28%) in study arm vs 20 (1.62%) in control arm. The pooled RR was 1.45 (95% CI: 0.82 –2.54, P = 0.20) and RD was 0.01 (95% CI: - 0.00 – 0.02, P = 0.08). Treatment discontinuation due to TRAE was noted in 419 (28.10%) vs 255 (20.66%) in control group with RR of 1.36 (95% CI: 1.19 –1.56, P < 0.0001) and RD of 0.08 (95% CI: - 0.04 – 0.11, P < 0.0001).
Conclusion
High-grade treatment-related adverse events were increased in front-line atezolizumab chemoimmunotherapy regimen and patients on the study arm experienced significant drop outs due to TRAE, despite showing survival benefits in studies. Good supportive care may enhance patients’ quality of life and compliance.
