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Miguel Quirch
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MA03 - Clinomics and Genomics (ID 119)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Heather A Wakelee, Wilfried Ernst Erich Eberhardt
- Coordinates: 9/08/2019, 10:30 - 12:00, Colorado Springs (1994)
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MA03.07 - First-Line Atezolizumab Chemoimmunotherapy in Advanced Non-Squamous NSCLC Patients Harboring EGFR/ALK Genetic Alterations (Now Available) (ID 1163)
10:30 - 12:00 | Author(s): Miguel Quirch
- Abstract
- Presentation
Background
Management of advanced non-squamous non-small cell lung cancer (NSCLC) is an area in dire need of therapeutic innovation. In recent years, multiple randomized clinical trials (RCT) have combined atezolizumab, programmed death ligand 1 (PDL-1) antibody, with chemotherapy as first-line treatment of advanced non-squamous NSCLC. In patients with EGFR/ ALK genetic alterations, PDL-1 or programmed death receptor 1 (PD-1) inhibitors monotherapy previously failed to demonstrate survival benefits compared to standard chemotherapy. The purpose of our study is to explore the efficacy of atezolizumab in combination with chemotherapy for first-line treatment of advanced non-squamous NSCLC harboring EGFR or ALK genetic alterations.
Method
We conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs utilizing first-line atezolizumab combination regimen in patients with advanced non-squamous NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q -statistic. Random effects model was applied.
Result
3 RCTs (IMpower – 130, 132 and 150) including 2101 patients with advanced non-squamous NSCLC were eligible. The study arm used standard chemotherapy regimens in combination with atezolizumab while control arm used only standard chemotherapy regimens. The randomization ratio was 2:1 in IMpower130 study and 2:1 in other studies. The I2statistic for heterogeneity was 0, suggesting homogeneity among RCTs. 1949 patients were EGFR/ ALK wild type and 152 patients from Impower 130 and 150 were positive for EGFR/ ALK genetic alterations. The pooled HR for PFS was statistically significant at 0.62 (95% CI: 0.56- 0.69; P < 0.0001) in patients with EGFR or ALK genetic alterations, favoring first-line atezolizumab chemoimmunotherapy regimen. In the EGFR/ ALK wild type population, the pooled HR for PFS was 0.63 (95% CI: 0.43 to 0.94; P = 0.02).
Conclusion
Our meta-analysis demonstrated that atezolizumab in combination with chemotherapy significantly improved progression-free survival compared to standard chemotherapy in patients with advanced non-squamous NSCLC, regardless of the presence or absence of EGFR/ ALK genetic alterations.
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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): Miguel Quirch
- 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.
