Virtual Library

Start Your Search

Sriman Swarup



Author of

  • +

    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
    • +

      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): Sriman Swarup

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA03 - Clinomics and Genomics (ID 119)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • +

      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): Sriman Swarup

      • Abstract
      • Presentation
      • Slides

      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.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    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
    • +

      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): Sriman Swarup

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 3
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
    • +

      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): Sriman Swarup

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      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): Sriman Swarup

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      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): Sriman Swarup

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.