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Tun Win Naing
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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): Tun Win Naing
- 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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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-09 - Immune-Related Adverse Events in Advanced Non-Squamous NSCLC Patients Treated with Upfront Checkpoint Inhibitors Combination (Now Available) (ID 1508)
10:15 - 18:15 | Author(s): Tun Win Naing
- Abstract
Background
Immune-related adverse events (IRAE) are a unique set of adverse events caused by checkpoint inhibitors due to enhanced activation of the immune system. IRAEs can virtually affect any organ system and have been responsible for significant morbidity, treatment delay, treatment discontinuation, and even death. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of IRAEs when checkpoint inhibitors were utilized as first-line in combination with chemotherapies in non-squamous non-small cell lung cancer (NSCLC) patients.
Method
We systematically conducted a literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. Phase 3 RCTs that mention IRAEs as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q -statistic. Random effects model was applied.
Result
2785 patients with advanced non-squamous NSCLC from 5 RCTs (Keynote – 021,189, IMpower – 130, 132 and 150) were eligible. The study arm used standard chemotherapy regimens in combination with pembrolizumab or atezolizumab while control arm utilized only standard chemotherapy regimens. The randomization ratio was 2:1 in IMpower-130 and Keynote-189 studies and 1:1 in other studies. The RR of all-grade side effects were as follows: hypothyroidism, 3.82 (95% CI: 2.14 – 6.80, p < 0.0001); hyperthyroidism, 2.58 (95% CI: 1.32– 5.04; p = 0.005); pneumonitis, 2.62 (95% CI: 1.58– 4.32; p = 0.0002); hepatitis, 3.75 (95% CI: 1.23 – 11.50, p = 0.02); colitis, 4.82 (95% CI: 1.67– 13.90; p = 0.004); and pancreatitis, 2.35 (95% CI: 0.75–7.41; p =0.14). The RR of high-grade side effects were as follows: hypothyroidism, 2.93 (95% CI: 0.62 – 13.74, p = 0.17); hyperthyroidism, 2.32 (95% CI: 0.37– 14.71; p = 0.37); pneumonitis, 1.65 (95% CI: 0.80– 3.41; p = 0.18); hepatitis, 4.14 (95% CI: 1.05 – 16.33, p = 0.04); colitis, 3.31 (95% CI: 1.02– 10.77; p = 0.05); and pancreatitis, 1.44 (95% CI: 0.29– 7.13; p = 0.65).
Conclusion
Patients on combined chemoimmunotherapy experienced a significant increase in all grades of hepatitis and colitis with a relative risk of 4.14 for grade 3 and 4 hepatitis. They also contributed to all-grade hypothyroidism, hyperthyroidism and pneumonitis. These toxicities have significant impact on patients’ quality of life, ultimately affecting patients’ compliance. A timely intervention with proper supportive care is necessary.
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P2.04-46 - Tolerability and Treatment-Related Adverse Events of Upfront Pembrolizumab Combination Regimens in Advanced NSCLC Patients (Now Available) (ID 1139)
10:15 - 18:15 | Author(s): Tun Win Naing
- Abstract
Background
Non-small cell lung cancer (NSCLC) accounts for approximately 80% of cases diagnosed with lung cancer. Pembrolizumab is a humanized IgG4 subtype antibody that targets programmed death receptor (PD-1) of lymphocytes. Recent studies have shown that addition of pembrolizumab to traditional chemotherapy regimens improves survival in advanced NSCLC. Nevertheless, there are considerable safety concerns, ultimately leading to significant morbidity affecting patients’ quality of life, and treatment discontinuation. 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
PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019 were queried. RCTs utilizing first-line pembrolizumab chemoimmunotherapy 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-test.
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 utilized only standard chemotherapy regimens. The randomization ratio was 2:1 in Keynote-189 study and 1:1 in other studies. The pooled RR of any-grade TRAE was not significant at 1.01 (95% CI: 0.99–1.02, P = 0.29) and RR of high-grade TRAE was 1.03 (95% CI: 0.95–1.12, P = 0.47). Yet, the relative risk of treatment discontinuation due to any-grade TRAE was statistically significant at 1.75 (95% CI: 1.26–2.45, P = 0.001) and RR of treatment discontinuation due to high-grade TRAE was 1.85 (95% CI: 1.38–2.49, P < 0.0001). Treatment-related deaths were reported as 51 (6.87%) in study arm vs 32 (5.88%) in control arm. The pooled RR was not significant at 1.18 (95% CI: 0.76–1.82, P = 0.46).
Conclusion
All grades of TRAE and treatment related deaths were not significantly increased in first-line pembrolizumab chemoimmunotherapy. However, patients on the study arm experienced significant drop-out due to TRAE, despite showing survival benefits in the studies. Proper supportive care may reduce unwanted treatment discontinuations and enhance patients’ compliance.
