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Rachana Yendala
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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): Rachana Yendala
- 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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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-78 - Efficacy of Checkpoint Inhibitors in Combination with Chemotherapy for First-Line Treatment of Advanced Non-Squamous NSCLC (Now Available) (ID 1168)
09:45 - 18:00 | Author(s): Rachana Yendala
- Abstract
Background
Checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab, or atezolizumab) have created a fundamental paradigm shift in the management of non-small cell lung cancer (NSCLC). In recent years, many randomized clinical trials (RCT) have combined different checkpoint inhibitors with various standard chemotherapy regimens as first-line treatment of advanced non-squamous NSCLC. In general, these trials have included patients across different levels of PD-L-1 expression. The purpose of our study is to consolidate the efficacy of checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced non- squamous NSCLC.
Method
We systematically conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs of first-line chemotherapy +/- immunotherapy 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 overall survival (OS) and progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q -statistic. Random effects model was applied.
Result
A total of 3228 patients with advanced non-squamous NSCLC from 6 RCTs (Keynote – 021,189, IMpower – 130, 132, 150, and Lynch et al.) and a subgroup of another RCT (Checkmate-227) were included. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, atezolizumab, or nivolumab while control arm used only standard chemotherapy regimens. The randomization ratio was 2:1 in IMpower-130 and Keynote-189 studies and 1:1 in other studies. The I2statistic for heterogeneity was 15, suggesting some heterogeneity among RCTs. The pooled HR for PFS was statistically significant at 0.61 (95% CI: 0.55-0.67; P < 0.00001), and the pooled HR for OS was noted at 0.78 (95% CI: 0.65- 0.94; P = 0.01).The PFS benefit was observed in all PD-L1 categories, including PD-L1 negative/ tumor proportion score (TPS) of less than 1% cohort (HR, 0.67; 95% CI: 0.53- 0.84; P = 0.0005), PD-L1 low/ TPS ≥1-49% cohort (HR, 0.62; 95% CI: 0.52- 0.74; P < 0.00001) and PD-L1 high/ TPS ≥ 50% cohort (HR, 0.42; 95% CI: 0.33- 0.52; P < 0.00001).
Conclusion
Our study showed that first-line checkpoint inhibitors in combination with chemotherapy significantly improved PFS and OS compared to standard chemotherapy in patients with advanced non-squamous NSCLC and the PFS benefit was consistent regardless of PD-L1 expression.
