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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): Somedeb Ball
- 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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P1.04 - 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): Somedeb Ball
- 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.
