A pooled analysis of two phase II trials evaluating metformin plus platinum-based chemotherapy in advanced non-small cell lung cancer

Anish B. Parikh, Kristen Marrone, Daniel J. Becker, Julie Brahmer, David S Ettinger, Benjamin Levy

Research output: Contribution to journalArticle

Abstract

Background: Despite a wealth of preclinical and observational data, prospective data regarding the use of metformin in lung cancer is extremely limited. Methods: We pooled individualized data from two prospective trials evaluating metformin plus platinum-based chemotherapy, with or without bevacizumab, in non-diabetic patients with untreated advanced NSCLC. In addition to reporting on clinical efficacy and safety endpoints, we also explored metformin's activity in key molecular cohorts. Results: 33 patients were included in the pooled analysis, of whom 70% were current or previous smokers. 82% had standard tissue molecular testing results available. KRAS, EGFR, and LKB1 mutation prevalence was 48%, 26%, and 8.3%, respectively. Composite median PFS was 6 months for all patients (95% CI: [1.36, 7.96]), 7.2 months for KRAS mutants (95% CI: [1.18, 9.21]), and 6.6 months for EGFR mutants (95% CI: [1.18, 15.29]). Composite median OS was 14.8 months for all patients (95% CI: [8.25, 19.99]), 17.5 months for KRAS mutants (95% CI: [8.86, 26.96]), and 13.3 months for EGFR mutants (95% CI: [2.60, 25.86]). Lymphopenia was the most common grade 3 AE (12%), followed by leukopenia, nausea, vomiting, and hypertension (9% each). There were 2 grade 4 AEs, neutropenia (21%) and sepsis (3%), and 1 grade 5 AE (colonic perforation) attributed to bevacizumab. Conclusion: Our results confirm the previously shown efficacy and tolerability of metformin in combination with chemotherapy and highlight encouraging activity in key molecular cohorts. Future efforts should build on this work by prospectively studying metformin in these molecular subgroups.

Original languageEnglish (US)
Article number100150
JournalCancer Treatment and Research Communications
Volume20
DOIs
StatePublished - Jan 1 2019

Fingerprint

Metformin
Platinum
Non-Small Cell Lung Carcinoma
Drug Therapy
Lymphopenia
Leukopenia
Combination Drug Therapy
Neutropenia
Nausea
Vomiting
Lung Neoplasms
Sepsis
Hypertension
Safety
Mutation
Bevacizumab

Keywords

  • Chemotherapy
  • Drug repositioning
  • Metformin
  • Non-small cell lung cancer
  • NSCLC
  • Repurposed therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{6402ec17afc14ab28ed61c9469e1fa8f,
title = "A pooled analysis of two phase II trials evaluating metformin plus platinum-based chemotherapy in advanced non-small cell lung cancer",
abstract = "Background: Despite a wealth of preclinical and observational data, prospective data regarding the use of metformin in lung cancer is extremely limited. Methods: We pooled individualized data from two prospective trials evaluating metformin plus platinum-based chemotherapy, with or without bevacizumab, in non-diabetic patients with untreated advanced NSCLC. In addition to reporting on clinical efficacy and safety endpoints, we also explored metformin's activity in key molecular cohorts. Results: 33 patients were included in the pooled analysis, of whom 70{\%} were current or previous smokers. 82{\%} had standard tissue molecular testing results available. KRAS, EGFR, and LKB1 mutation prevalence was 48{\%}, 26{\%}, and 8.3{\%}, respectively. Composite median PFS was 6 months for all patients (95{\%} CI: [1.36, 7.96]), 7.2 months for KRAS mutants (95{\%} CI: [1.18, 9.21]), and 6.6 months for EGFR mutants (95{\%} CI: [1.18, 15.29]). Composite median OS was 14.8 months for all patients (95{\%} CI: [8.25, 19.99]), 17.5 months for KRAS mutants (95{\%} CI: [8.86, 26.96]), and 13.3 months for EGFR mutants (95{\%} CI: [2.60, 25.86]). Lymphopenia was the most common grade 3 AE (12{\%}), followed by leukopenia, nausea, vomiting, and hypertension (9{\%} each). There were 2 grade 4 AEs, neutropenia (21{\%}) and sepsis (3{\%}), and 1 grade 5 AE (colonic perforation) attributed to bevacizumab. Conclusion: Our results confirm the previously shown efficacy and tolerability of metformin in combination with chemotherapy and highlight encouraging activity in key molecular cohorts. Future efforts should build on this work by prospectively studying metformin in these molecular subgroups.",
keywords = "Chemotherapy, Drug repositioning, Metformin, Non-small cell lung cancer, NSCLC, Repurposed therapy",
author = "Parikh, {Anish B.} and Kristen Marrone and Becker, {Daniel J.} and Julie Brahmer and Ettinger, {David S} and Benjamin Levy",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.ctarc.2019.100150",
language = "English (US)",
volume = "20",
journal = "Cancer Treatment and Research Communications",
issn = "2213-0896",
publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - A pooled analysis of two phase II trials evaluating metformin plus platinum-based chemotherapy in advanced non-small cell lung cancer

AU - Parikh, Anish B.

AU - Marrone, Kristen

AU - Becker, Daniel J.

AU - Brahmer, Julie

AU - Ettinger, David S

AU - Levy, Benjamin

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Despite a wealth of preclinical and observational data, prospective data regarding the use of metformin in lung cancer is extremely limited. Methods: We pooled individualized data from two prospective trials evaluating metformin plus platinum-based chemotherapy, with or without bevacizumab, in non-diabetic patients with untreated advanced NSCLC. In addition to reporting on clinical efficacy and safety endpoints, we also explored metformin's activity in key molecular cohorts. Results: 33 patients were included in the pooled analysis, of whom 70% were current or previous smokers. 82% had standard tissue molecular testing results available. KRAS, EGFR, and LKB1 mutation prevalence was 48%, 26%, and 8.3%, respectively. Composite median PFS was 6 months for all patients (95% CI: [1.36, 7.96]), 7.2 months for KRAS mutants (95% CI: [1.18, 9.21]), and 6.6 months for EGFR mutants (95% CI: [1.18, 15.29]). Composite median OS was 14.8 months for all patients (95% CI: [8.25, 19.99]), 17.5 months for KRAS mutants (95% CI: [8.86, 26.96]), and 13.3 months for EGFR mutants (95% CI: [2.60, 25.86]). Lymphopenia was the most common grade 3 AE (12%), followed by leukopenia, nausea, vomiting, and hypertension (9% each). There were 2 grade 4 AEs, neutropenia (21%) and sepsis (3%), and 1 grade 5 AE (colonic perforation) attributed to bevacizumab. Conclusion: Our results confirm the previously shown efficacy and tolerability of metformin in combination with chemotherapy and highlight encouraging activity in key molecular cohorts. Future efforts should build on this work by prospectively studying metformin in these molecular subgroups.

AB - Background: Despite a wealth of preclinical and observational data, prospective data regarding the use of metformin in lung cancer is extremely limited. Methods: We pooled individualized data from two prospective trials evaluating metformin plus platinum-based chemotherapy, with or without bevacizumab, in non-diabetic patients with untreated advanced NSCLC. In addition to reporting on clinical efficacy and safety endpoints, we also explored metformin's activity in key molecular cohorts. Results: 33 patients were included in the pooled analysis, of whom 70% were current or previous smokers. 82% had standard tissue molecular testing results available. KRAS, EGFR, and LKB1 mutation prevalence was 48%, 26%, and 8.3%, respectively. Composite median PFS was 6 months for all patients (95% CI: [1.36, 7.96]), 7.2 months for KRAS mutants (95% CI: [1.18, 9.21]), and 6.6 months for EGFR mutants (95% CI: [1.18, 15.29]). Composite median OS was 14.8 months for all patients (95% CI: [8.25, 19.99]), 17.5 months for KRAS mutants (95% CI: [8.86, 26.96]), and 13.3 months for EGFR mutants (95% CI: [2.60, 25.86]). Lymphopenia was the most common grade 3 AE (12%), followed by leukopenia, nausea, vomiting, and hypertension (9% each). There were 2 grade 4 AEs, neutropenia (21%) and sepsis (3%), and 1 grade 5 AE (colonic perforation) attributed to bevacizumab. Conclusion: Our results confirm the previously shown efficacy and tolerability of metformin in combination with chemotherapy and highlight encouraging activity in key molecular cohorts. Future efforts should build on this work by prospectively studying metformin in these molecular subgroups.

KW - Chemotherapy

KW - Drug repositioning

KW - Metformin

KW - Non-small cell lung cancer

KW - NSCLC

KW - Repurposed therapy

UR - http://www.scopus.com/inward/record.url?scp=85065566365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065566365&partnerID=8YFLogxK

U2 - 10.1016/j.ctarc.2019.100150

DO - 10.1016/j.ctarc.2019.100150

M3 - Article

VL - 20

JO - Cancer Treatment and Research Communications

JF - Cancer Treatment and Research Communications

SN - 2213-0896

M1 - 100150

ER -