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Srikala Meda
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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): Srikala Meda
- 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: 1
- 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): Srikala Meda
- 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.
