Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies

Christian Schulz, David R Gandara, Carmen G. Berardo, Rachel Rosenthal, Jason Foo, Chaienna Morel, Marcus Ballinger, Claire Watkins, Paula Chu

Research output: Contribution to journalArticle

Abstract

Background: Extended onset of treatment effect and longer-term survival with anti–programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) immunotherapies, atezolizumab, nivolumab, and pembrolizumab, have changed the landscape of second- or subsequent-line (2L+) treatments for adults with non–small-cell lung cancer (NSCLC). This systematic literature review included phase I to IV randomized, controlled trials of 2L+ NSCLC therapies from MEDLINE, Embase, and secondary sources. Materials and Methods: Studies of treatments approved in the European Union or United States had to be in English with ≥ 10 patients per arm. A fractional polynomials network meta-analysis (NMA) was conducted because traditional NMA of hazard ratios does not account for delayed onset of clinical effect or long-term survival observed in PD-L1/PD-1 inhibitor trials. Adjusted analyses accounted for treatment switching in the atezolizumab OAK trial. Expected survival time reflected area under the curve over the time horizon. Expected overall survival (OS) was ranked by median ranking with 95% credible intervals and by surface under the cumulative ranking curve. Of 25,115 screened records, 28 studies were included in the quantitative analyses of OS and progression-free survival. Results: PD-L1/PD-1 inhibitors had comparable expected 5-year OS; all performed better than other treatment options. In unadjusted analyses, surface under the cumulative ranking curve ranked nivolumab first (87.9%), followed by atezolizumab (85.8%) and pembrolizumab (82.8%). Analyses adjusted for patients switching from docetaxel to immunotherapy ranked atezolizumab first (89.6%), followed by nivolumab (86.5%) and pembrolizumab (81.9%). Conclusion: This NMA applied an appropriate approach for indirect comparisons, including cancer immunotherapies, and supported robustness of PD-L1/PD-1 immunotherapies for 2L+ treatment of NSCLC.

Original languageEnglish (US)
JournalClinical lung cancer
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Non-Small Cell Lung Carcinoma
Immunotherapy
Survival
Neoplasms
docetaxel
Therapeutics
Programmed Cell Death 1 Receptor
European Union
Survival Analysis
Network Meta-Analysis
MEDLINE
Disease-Free Survival
Area Under Curve
Randomized Controlled Trials
Ligands
MPDL3280A
nivolumab
pembrolizumab

Keywords

  • Atezolizumab
  • Nivolumab
  • Overall survival
  • Pembrolizumab
  • Programmed cell death 1 ligand 1

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC : A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies. / Schulz, Christian; Gandara, David R; Berardo, Carmen G.; Rosenthal, Rachel; Foo, Jason; Morel, Chaienna; Ballinger, Marcus; Watkins, Claire; Chu, Paula.

In: Clinical lung cancer, 01.01.2019.

Research output: Contribution to journalArticle

Schulz, Christian ; Gandara, David R ; Berardo, Carmen G. ; Rosenthal, Rachel ; Foo, Jason ; Morel, Chaienna ; Ballinger, Marcus ; Watkins, Claire ; Chu, Paula. / Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC : A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies. In: Clinical lung cancer. 2019.
@article{0280baecf2b84817bb001c900b79456b,
title = "Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies",
abstract = "Background: Extended onset of treatment effect and longer-term survival with anti–programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) immunotherapies, atezolizumab, nivolumab, and pembrolizumab, have changed the landscape of second- or subsequent-line (2L+) treatments for adults with non–small-cell lung cancer (NSCLC). This systematic literature review included phase I to IV randomized, controlled trials of 2L+ NSCLC therapies from MEDLINE, Embase, and secondary sources. Materials and Methods: Studies of treatments approved in the European Union or United States had to be in English with ≥ 10 patients per arm. A fractional polynomials network meta-analysis (NMA) was conducted because traditional NMA of hazard ratios does not account for delayed onset of clinical effect or long-term survival observed in PD-L1/PD-1 inhibitor trials. Adjusted analyses accounted for treatment switching in the atezolizumab OAK trial. Expected survival time reflected area under the curve over the time horizon. Expected overall survival (OS) was ranked by median ranking with 95{\%} credible intervals and by surface under the cumulative ranking curve. Of 25,115 screened records, 28 studies were included in the quantitative analyses of OS and progression-free survival. Results: PD-L1/PD-1 inhibitors had comparable expected 5-year OS; all performed better than other treatment options. In unadjusted analyses, surface under the cumulative ranking curve ranked nivolumab first (87.9{\%}), followed by atezolizumab (85.8{\%}) and pembrolizumab (82.8{\%}). Analyses adjusted for patients switching from docetaxel to immunotherapy ranked atezolizumab first (89.6{\%}), followed by nivolumab (86.5{\%}) and pembrolizumab (81.9{\%}). Conclusion: This NMA applied an appropriate approach for indirect comparisons, including cancer immunotherapies, and supported robustness of PD-L1/PD-1 immunotherapies for 2L+ treatment of NSCLC.",
keywords = "Atezolizumab, Nivolumab, Overall survival, Pembrolizumab, Programmed cell death 1 ligand 1",
author = "Christian Schulz and Gandara, {David R} and Berardo, {Carmen G.} and Rachel Rosenthal and Jason Foo and Chaienna Morel and Marcus Ballinger and Claire Watkins and Paula Chu",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.cllc.2019.06.017",
language = "English (US)",
journal = "Clinical Lung Cancer",
issn = "1525-7304",
publisher = "Elsevier",

}

TY - JOUR

T1 - Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC

T2 - A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies

AU - Schulz, Christian

AU - Gandara, David R

AU - Berardo, Carmen G.

AU - Rosenthal, Rachel

AU - Foo, Jason

AU - Morel, Chaienna

AU - Ballinger, Marcus

AU - Watkins, Claire

AU - Chu, Paula

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Extended onset of treatment effect and longer-term survival with anti–programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) immunotherapies, atezolizumab, nivolumab, and pembrolizumab, have changed the landscape of second- or subsequent-line (2L+) treatments for adults with non–small-cell lung cancer (NSCLC). This systematic literature review included phase I to IV randomized, controlled trials of 2L+ NSCLC therapies from MEDLINE, Embase, and secondary sources. Materials and Methods: Studies of treatments approved in the European Union or United States had to be in English with ≥ 10 patients per arm. A fractional polynomials network meta-analysis (NMA) was conducted because traditional NMA of hazard ratios does not account for delayed onset of clinical effect or long-term survival observed in PD-L1/PD-1 inhibitor trials. Adjusted analyses accounted for treatment switching in the atezolizumab OAK trial. Expected survival time reflected area under the curve over the time horizon. Expected overall survival (OS) was ranked by median ranking with 95% credible intervals and by surface under the cumulative ranking curve. Of 25,115 screened records, 28 studies were included in the quantitative analyses of OS and progression-free survival. Results: PD-L1/PD-1 inhibitors had comparable expected 5-year OS; all performed better than other treatment options. In unadjusted analyses, surface under the cumulative ranking curve ranked nivolumab first (87.9%), followed by atezolizumab (85.8%) and pembrolizumab (82.8%). Analyses adjusted for patients switching from docetaxel to immunotherapy ranked atezolizumab first (89.6%), followed by nivolumab (86.5%) and pembrolizumab (81.9%). Conclusion: This NMA applied an appropriate approach for indirect comparisons, including cancer immunotherapies, and supported robustness of PD-L1/PD-1 immunotherapies for 2L+ treatment of NSCLC.

AB - Background: Extended onset of treatment effect and longer-term survival with anti–programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) immunotherapies, atezolizumab, nivolumab, and pembrolizumab, have changed the landscape of second- or subsequent-line (2L+) treatments for adults with non–small-cell lung cancer (NSCLC). This systematic literature review included phase I to IV randomized, controlled trials of 2L+ NSCLC therapies from MEDLINE, Embase, and secondary sources. Materials and Methods: Studies of treatments approved in the European Union or United States had to be in English with ≥ 10 patients per arm. A fractional polynomials network meta-analysis (NMA) was conducted because traditional NMA of hazard ratios does not account for delayed onset of clinical effect or long-term survival observed in PD-L1/PD-1 inhibitor trials. Adjusted analyses accounted for treatment switching in the atezolizumab OAK trial. Expected survival time reflected area under the curve over the time horizon. Expected overall survival (OS) was ranked by median ranking with 95% credible intervals and by surface under the cumulative ranking curve. Of 25,115 screened records, 28 studies were included in the quantitative analyses of OS and progression-free survival. Results: PD-L1/PD-1 inhibitors had comparable expected 5-year OS; all performed better than other treatment options. In unadjusted analyses, surface under the cumulative ranking curve ranked nivolumab first (87.9%), followed by atezolizumab (85.8%) and pembrolizumab (82.8%). Analyses adjusted for patients switching from docetaxel to immunotherapy ranked atezolizumab first (89.6%), followed by nivolumab (86.5%) and pembrolizumab (81.9%). Conclusion: This NMA applied an appropriate approach for indirect comparisons, including cancer immunotherapies, and supported robustness of PD-L1/PD-1 immunotherapies for 2L+ treatment of NSCLC.

KW - Atezolizumab

KW - Nivolumab

KW - Overall survival

KW - Pembrolizumab

KW - Programmed cell death 1 ligand 1

UR - http://www.scopus.com/inward/record.url?scp=85069815142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069815142&partnerID=8YFLogxK

U2 - 10.1016/j.cllc.2019.06.017

DO - 10.1016/j.cllc.2019.06.017

M3 - Article

AN - SCOPUS:85069815142

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

SN - 1525-7304

ER -