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Kelvin K.W. Chan



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-16 - First-Line Pembrolizumab With or Without Chemotherapy in PD-L1 positive NSCLC: A Network Meta-Analysis of Randomized Trials. (ID 12147)

      16:45 - 18:00  |  Author(s): Kelvin K.W. Chan

      • Abstract

      Background

      Pembrolizumab has replaced platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression >/=50%. Among PD-L1 unselected patients, pembrolizumab + chemotherapy is superior to chemotherapy alone. This network meta-analysis compared pembrolizumab alone with pembrolizumab + chemotherapy in patients with >/=50% PD-L1 positive NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Using the Keynote 024 and 189 (PD-L1 >/=50% subgroup) trials, an indirect network was constructed to compare pembrolizumab and pembrolizumab + chemotherapy through the chemotherapy control arms of each trial. Baseline characteristics and chemotherapy outcomes in both trials were examined for heterogeneity. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs) including immune-related adverse events (irAE) were extracted from trial results. AE results were unavailable for the PD-L1 >/=50% subgroup of KN189, so overall AE results were used. Comparisons were expressed as hazard ratios (HRs) for survival outcomes, and as risk difference (RD) for ORR and toxicity.

      4c3880bb027f159e801041b1021e88e8 Result

      507 patients were included: 154 on pembrolizumab, 357 on chemotherapy and 410 on combination. Baseline characteristics of patients in both trials were similar in age, sex, performance status and smoking history. Both trials also had similar chemotherapy outcomes (PFS 6 vs 5 mos) suggesting similar patient prognosis. Network meta-analysis showed no difference between pembrolizumab + chemotherapy and pembrolizumab alone in OS (HR 0.70, 95%CI 0.38-1.30, p=0.26) or PFS (HR 0.72, 95%CI 0.45-1.16, p=0.18), but combination therapy was associated with higher ORR (+21.5%, 95%CI 4.83-38.2%, p=0.011). Overall and grade 3-5 AE rates were higher with combination treatment compared with pembrolizumab alone, but irAE appeared less common with combination treatment (table).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Among patients with >/=50% PD-L1 positive NSCLC, pembrolizumab + chemotherapy did not improve OS or PFS compared with pembrolizumab alone, but was associated with higher ORR. Lower rates of irAE with combination therapy are interesting and warrant further study.

      Adverse events for Pembrolizumab + Chemotherapy vs Pembrolizumab Alone

      All Grade Adverse Events

      Grade 3-5 Adverse Events

      Risk Difference (%)

      95% CI

      p-value

      Risk Difference (%)

      95% CI

      p-value

      Any

      17.4

      8.8, 26.0

      <0.001

      18.2

      4.8, 31.5

      0.008

      Led to Discontinuation

      9.4

      1.3, 17.6

      0.023

      5.7

      -1.2, 12.7

      0.11

      Led to Death

      2.1

      -2.7, 6.9

      0.40

      2.1

      -2.7, 6.9

      0.40

      Nausea

      37.2

      24.7, 49.7

      <0.001

      2.0

      -1.8, 5.8

      0.31

      Anemia

      38.4

      26.4, 50.5

      <0.001

      18.3

      9.2, 27.4

      <0.001

      Fatigue

      20.9

      8.9, 32.9

      <0.001

      5.2

      0.6, 9.8

      0.025

      Decreased appetite

      14.9

      3.5, 26.2

      0.01

      3.7

      0.7, 6.7

      0.017

      Diarrhea

      8.6

      -2.0, 19.2

      0.11

      -0.4

      -5.1, 4.4

      0.89

      Neutropenia

      24.9

      14.9, 34.9

      <0.001

      17.3

      9.4, 25.1

      <0.001

      Vomiting

      18.3

      8.4, 28.3

      <0.001

      0.8

      -2.7, 4.2

      0.67

      Pyrexia

      -0.4

      -9.1, 8.3

      0.93

      NA

      Constipation

      10.6

      0.7, 20.5

      0.036

      NA

      Thrombocytopenia

      15

      7.1, 23.0

      <0.001

      6.3

      0.6, 12.0

      0.029

      All Grade Immune-Related Adverse Events

      Grade 3-5 Immune-Related Adverse Events

      Any

      -13.7

      -23.7, -3.74

      0.007

      -4.6

      -11.2, 1.6

      0.15

      Hypothyroidism

      -3.6

      -9.4, 2.3

      0.23

      NA

      Hyperthyroidism

      -5.5

      -11, 0.1

      0.051

      NA

      Pneumonitis

      -3.2

      -8.1, 1.7

      0.20

      -1.2

      -5, 2.5

      0.54

      Infusion reaction

      -1.7

      -6.0, 2.5

      0.43

      NA

      Severe skin reaction

      -4.4

      -8.4, -4.3

      0.03

      -0.4

      -7.8, -0.1

      0.047

      Colitis

      0.3

      -2.3, 2.9

      0.84

      -0.6

      -2.5, 1.4

      0.58

      Myositis

      -1.7

      -3.9, 0.5

      0.14

      NA

      Hypophysitis

      0.1

      -1.4, 1.6

      0.91

      NA

      Nephritis

      1.1

      -0.7, 2.9

      0.24

      0.8

      -0.9, 2.6

      0.35
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