Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma

NVALT Study Group; Christi M J Steendam; Robert Peric; Nico C van Walree; Magdolen Youssef; Franz M N H Schramel; Pepijn Brocken; John W G van Putten; Vincent van der Noort; G D Marijn Veerman; Stijn L W Koolen; Harry J M Groen; Anne-Marie C Dingemans; Ron H J Mathijssen; Egbert F Smit; Joachim G J V Aerts

doi:10.1016/j.lungcan.2021.08.002

Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma

NVALT Study Group, Christi M J Steendam, Robert Peric, Nico C van Walree, Magdolen Youssef, Franz M N H Schramel, Pepijn Brocken, John W G van Putten, Vincent van der Noort, G D Marijn Veerman, Stijn L W Koolen, Harry J M Groen, Anne-Marie C Dingemans, Ron H J Mathijssen, Egbert F Smit, Joachim G J V Aerts^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Earlier preclinical and phase II research showed enhanced effect of docetaxel plus intercalated erlotinib. The NVALT-18 phase III study was designed to compare docetaxel with docetaxel plus intercalated erlotinib in relapsed metastasized non-squamous (NSQ) non-small cell lung cancer (NSCLC).

Methods: Patients with relapsed Epidermal Growth Factor Receptor (EGFR) wild type (WT) NSQ-NSCLC were randomized 1:1 to docetaxel 75 mg/m(2) intravenously on day 1 every 21 days (control), or docetaxel 75 mg/m(2) intravenously on day 1 plus erlotinib 150 mg/day orally on day 2-16 every 21 days (experimental arm). Progression free survival (PFS) was the primary endpoint, secondary objectives were duration of response, overall survival (OS) and toxicity.

Results: Between October 2016 and April 2018 a total of 45 patients were randomized and received treatment in the control (N = 23) or experimental arm (N = 22), the study was stopped due to slow accrual. Median PFS was 4.0 months (95% CI: 1.5-7.1) versus 1.9 months (95% CI 1.4-3.5), p = 0.01 respectively; adjusted hazard ratio (HR) 2.51 (95% CI: 1.16-5.43). Corresponding median OS was 10.6 months (95% CI: 7.0-8.6) versus 4.7 months (95% CI: 3.2-8.6), p = 0.004, with an adjusted HR of 3.67 (95% CI: 1.46-9.27). Toxicity was higher with combination therapy, with toxicity >= CTCAE grade 3 in N = 6 (26%) in the control arm and N = 17 (77%) in the experimental arm (p < 0.001), mainly consisting of gastrointestinal symptoms and leukopenia.

Conclusions: Our study shows detrimental effects of docetaxel plus intercalated erlotinib, and strongly discourages further exploration of this combination in clinical practice.

Original language	English
Pages (from-to)	44-49
Number of pages	6
Journal	Lung Cancer
Volume	160
DOIs	https://doi.org/10.1016/j.lungcan.2021.08.002
Publication status	Published - Oct-2021

Keywords

Antineoplastic Combined Chemotherapy Protocols/adverse effects
Carcinoma, Non-Small-Cell Lung/drug therapy
Disease-Free Survival
Docetaxel/therapeutic use
Erlotinib Hydrochloride/therapeutic use
Humans
Lung Neoplasms/drug therapy
Quinazolines/therapeutic use
Taxoids/therapeutic use

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NVALT Study Group, Steendam, C. M. J., Peric, R., van Walree, N. C., Youssef, M., Schramel, F. M. N. H., Brocken, P., van Putten, J. W. G., van der Noort, V., Veerman, G. D. M., Koolen, S. L. W., Groen, H. J. M., Dingemans, A.-M. C., Mathijssen, R. H. J., Smit, E. F., & Aerts, J. G. J. V. (2021). Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma. Lung Cancer, 160, 44-49. https://doi.org/10.1016/j.lungcan.2021.08.002

@article{805bc8e635d14986a82e137b980eba50,

title = "Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma",

abstract = "Background: Earlier preclinical and phase II research showed enhanced effect of docetaxel plus intercalated erlotinib. The NVALT-18 phase III study was designed to compare docetaxel with docetaxel plus intercalated erlotinib in relapsed metastasized non-squamous (NSQ) non-small cell lung cancer (NSCLC).Methods: Patients with relapsed Epidermal Growth Factor Receptor (EGFR) wild type (WT) NSQ-NSCLC were randomized 1:1 to docetaxel 75 mg/m(2) intravenously on day 1 every 21 days (control), or docetaxel 75 mg/m(2) intravenously on day 1 plus erlotinib 150 mg/day orally on day 2-16 every 21 days (experimental arm). Progression free survival (PFS) was the primary endpoint, secondary objectives were duration of response, overall survival (OS) and toxicity.Results: Between October 2016 and April 2018 a total of 45 patients were randomized and received treatment in the control (N = 23) or experimental arm (N = 22), the study was stopped due to slow accrual. Median PFS was 4.0 months (95% CI: 1.5-7.1) versus 1.9 months (95% CI 1.4-3.5), p = 0.01 respectively; adjusted hazard ratio (HR) 2.51 (95% CI: 1.16-5.43). Corresponding median OS was 10.6 months (95% CI: 7.0-8.6) versus 4.7 months (95% CI: 3.2-8.6), p = 0.004, with an adjusted HR of 3.67 (95% CI: 1.46-9.27). Toxicity was higher with combination therapy, with toxicity >= CTCAE grade 3 in N = 6 (26%) in the control arm and N = 17 (77%) in the experimental arm (p < 0.001), mainly consisting of gastrointestinal symptoms and leukopenia.Conclusions: Our study shows detrimental effects of docetaxel plus intercalated erlotinib, and strongly discourages further exploration of this combination in clinical practice.",

keywords = "Antineoplastic Combined Chemotherapy Protocols/adverse effects, Carcinoma, Non-Small-Cell Lung/drug therapy, Disease-Free Survival, Docetaxel/therapeutic use, Erlotinib Hydrochloride/therapeutic use, Humans, Lung Neoplasms/drug therapy, Quinazolines/therapeutic use, Taxoids/therapeutic use",

author = "{NVALT Study Group} and Steendam, {Christi M J} and Robert Peric and {van Walree}, {Nico C} and Magdolen Youssef and Schramel, {Franz M N H} and Pepijn Brocken and {van Putten}, {John W G} and {van der Noort}, Vincent and Veerman, {G D Marijn} and Koolen, {Stijn L W} and Groen, {Harry J M} and Dingemans, {Anne-Marie C} and Mathijssen, {Ron H J} and Smit, {Egbert F} and Aerts, {Joachim G J V}",

year = "2021",

month = oct,

doi = "10.1016/j.lungcan.2021.08.002",

language = "English",

volume = "160",

pages = "44--49",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "ELSEVIER IRELAND LTD",

}

NVALT Study Group, Steendam, CMJ, Peric, R, van Walree, NC, Youssef, M, Schramel, FMNH, Brocken, P, van Putten, JWG, van der Noort, V, Veerman, GDM, Koolen, SLW, Groen, HJM, Dingemans, A-MC, Mathijssen, RHJ, Smit, EF & Aerts, JGJV 2021, 'Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma', Lung Cancer, vol. 160, pp. 44-49. https://doi.org/10.1016/j.lungcan.2021.08.002

TY - JOUR

T1 - Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma

AU - NVALT Study Group

AU - Steendam, Christi M J

AU - Peric, Robert

AU - van Walree, Nico C

AU - Youssef, Magdolen

AU - Schramel, Franz M N H

AU - Brocken, Pepijn

AU - van Putten, John W G

AU - van der Noort, Vincent

AU - Veerman, G D Marijn

AU - Koolen, Stijn L W

AU - Groen, Harry J M

AU - Dingemans, Anne-Marie C

AU - Mathijssen, Ron H J

AU - Smit, Egbert F

AU - Aerts, Joachim G J V

PY - 2021/10

Y1 - 2021/10

N2 - Background: Earlier preclinical and phase II research showed enhanced effect of docetaxel plus intercalated erlotinib. The NVALT-18 phase III study was designed to compare docetaxel with docetaxel plus intercalated erlotinib in relapsed metastasized non-squamous (NSQ) non-small cell lung cancer (NSCLC).Methods: Patients with relapsed Epidermal Growth Factor Receptor (EGFR) wild type (WT) NSQ-NSCLC were randomized 1:1 to docetaxel 75 mg/m(2) intravenously on day 1 every 21 days (control), or docetaxel 75 mg/m(2) intravenously on day 1 plus erlotinib 150 mg/day orally on day 2-16 every 21 days (experimental arm). Progression free survival (PFS) was the primary endpoint, secondary objectives were duration of response, overall survival (OS) and toxicity.Results: Between October 2016 and April 2018 a total of 45 patients were randomized and received treatment in the control (N = 23) or experimental arm (N = 22), the study was stopped due to slow accrual. Median PFS was 4.0 months (95% CI: 1.5-7.1) versus 1.9 months (95% CI 1.4-3.5), p = 0.01 respectively; adjusted hazard ratio (HR) 2.51 (95% CI: 1.16-5.43). Corresponding median OS was 10.6 months (95% CI: 7.0-8.6) versus 4.7 months (95% CI: 3.2-8.6), p = 0.004, with an adjusted HR of 3.67 (95% CI: 1.46-9.27). Toxicity was higher with combination therapy, with toxicity >= CTCAE grade 3 in N = 6 (26%) in the control arm and N = 17 (77%) in the experimental arm (p < 0.001), mainly consisting of gastrointestinal symptoms and leukopenia.Conclusions: Our study shows detrimental effects of docetaxel plus intercalated erlotinib, and strongly discourages further exploration of this combination in clinical practice.

AB - Background: Earlier preclinical and phase II research showed enhanced effect of docetaxel plus intercalated erlotinib. The NVALT-18 phase III study was designed to compare docetaxel with docetaxel plus intercalated erlotinib in relapsed metastasized non-squamous (NSQ) non-small cell lung cancer (NSCLC).Methods: Patients with relapsed Epidermal Growth Factor Receptor (EGFR) wild type (WT) NSQ-NSCLC were randomized 1:1 to docetaxel 75 mg/m(2) intravenously on day 1 every 21 days (control), or docetaxel 75 mg/m(2) intravenously on day 1 plus erlotinib 150 mg/day orally on day 2-16 every 21 days (experimental arm). Progression free survival (PFS) was the primary endpoint, secondary objectives were duration of response, overall survival (OS) and toxicity.Results: Between October 2016 and April 2018 a total of 45 patients were randomized and received treatment in the control (N = 23) or experimental arm (N = 22), the study was stopped due to slow accrual. Median PFS was 4.0 months (95% CI: 1.5-7.1) versus 1.9 months (95% CI 1.4-3.5), p = 0.01 respectively; adjusted hazard ratio (HR) 2.51 (95% CI: 1.16-5.43). Corresponding median OS was 10.6 months (95% CI: 7.0-8.6) versus 4.7 months (95% CI: 3.2-8.6), p = 0.004, with an adjusted HR of 3.67 (95% CI: 1.46-9.27). Toxicity was higher with combination therapy, with toxicity >= CTCAE grade 3 in N = 6 (26%) in the control arm and N = 17 (77%) in the experimental arm (p < 0.001), mainly consisting of gastrointestinal symptoms and leukopenia.Conclusions: Our study shows detrimental effects of docetaxel plus intercalated erlotinib, and strongly discourages further exploration of this combination in clinical practice.

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Carcinoma, Non-Small-Cell Lung/drug therapy

KW - Disease-Free Survival

KW - Docetaxel/therapeutic use

KW - Erlotinib Hydrochloride/therapeutic use

KW - Humans

KW - Lung Neoplasms/drug therapy

KW - Quinazolines/therapeutic use

KW - Taxoids/therapeutic use

U2 - 10.1016/j.lungcan.2021.08.002

DO - 10.1016/j.lungcan.2021.08.002

M3 - Article

C2 - 34403911

SN - 0169-5002

VL - 160

SP - 44

EP - 49

JO - Lung Cancer

JF - Lung Cancer

ER -

Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma

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Keywords

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