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Nimesh Adhikari
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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): Nimesh Adhikari
- 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.
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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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P2.04-46 - 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): Nimesh Adhikari
- 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.
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P2.04-86 - Efficacy of Ipilimumab in Combination with Chemotherapy for First-Line Treatment of Advanced Lung Cancer (Now Available) (ID 1990)
10:15 - 18:15 | Author(s): Nimesh Adhikari
- Abstract
Background
Lung cancer is the second most common cancer in both sexes and is the leading cause of cancer mortality in the United States. Combination of checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab, or atezolizumab) and chemotherapy has shown synergistic anti-tumor activities and has created a fundamental paradigm shift in the management of first-line treatment of advanced lung cancer. We performed a systematic review and meta-analysis of currently available randomized controlled trials (RCTs) to evaluate the efficacy of ipilimumab in combination with chemotherapy for the first-line treatment of advanced lung cancer.
Method
We systematically conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs utilizing first-line ipilimumab chemoimmunotherapy in patients with advanced lung cancer 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 3178 patients with advanced lung cancer from 5 RCTs were included in the analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab while control arm used only standard chemotherapy regimens. The randomization ratio was 1:1 in all studies. Ipilimumab was employed either in phased or concurrent with chemotherapy. The I2statistic for heterogeneity was 63%, suggesting some heterogeneity among RCTs. The pooled HR for PFS was significant at 0.85 (95% CI: 0.78-0.93; P = 0.0004) when ipilimumab was utilized in phased with chemotherapy. In non-small cell lung cancer population, the pooled HR for PFS was noted at 0.82 (95% CI: 0.68-1.00; P = 0.05), and the pooled HR for OS was 0.92 (95% CI: 0.83- 1.02; P = 0.10). In patients with extensive-stage small cell lung cancer, the pooled HR for PFS was statistically significant at 0.86 (95% CI: 0.77-0.97; P = 0.01), and the pooled HR for OS was 0.92 (95% CI: 0.81-1.06; P = 0.26).
Conclusion
Our meta-analysis depicted that upfront ipilimumab chemoimmunotherapy significantly improved PFS compared to standard chemotherapy, when ipilimumab was either employed in phased with chemotherapy or in patients with extensive-stage small cell lung cancer.
