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

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: 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.

Authors 15

1. Christi M. J. Steendam

   Erasmus MC · Amphia Ziekenhuis · Erasmus MC Cancer Institute

   Affiliation as printed

   Department of Pulmonary Diseases, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands; Department of Pulmonary Diseases, Amphia Hospital Breda, Molengracht 21, 4818 CK, the Netherlands

   Department of Pulmonary Diseases, Amphia Hospital Breda, Molengracht 21, 4818 CK, the Netherlands

   Department of Pulmonary Diseases, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands

2. Robert Peric

   Erasmus MC · Erasmus MC Cancer Institute

   Affiliation as printed

   Department of Pulmonary Diseases, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands

3. Nico C. van Walree

   Amphia Ziekenhuis

   Affiliation as printed

   Department of Pulmonary Diseases, Amphia Hospital Breda, Molengracht 21, 4818 CK, the Netherlands

4. Magdolen Youssef

   Máxima Medisch Centrum

   Affiliation as printed

   Department of Pulmonary Diseases, Máxima Medical Center Veldhoven, De Run 4600, 5504 DB, the Netherlands

5. Franz M.N.H. Schramel

   St. Antonius Ziekenhuis

   Affiliation as printed

   Department of Pulmonary Diseases, Antonius Hospital Nieuwegein, Koekoekslaan 1, 3435 CM, the Netherlands

6. Pepijn Brocken

   Haga Hospital

   Affiliation as printed

   Department of Pulmonary Diseases, Haga Hospital The Hague, Els Borst-Eilersplein 275, 2545 AA, the Netherlands

7. John W.G. van Putten

   Martini Ziekenhuis

   Affiliation as printed

   Department of Pulmonary Diseases, Martini Hospital Groningen, Van Swietenplein 1, 9728 NT, the Netherlands

8. Vincent van der Noort

   The Netherlands Cancer Institute

   Affiliation as printed

   Department of Biometrics, Netherlands Cancer Institute -Antoni van Leeuwenhoek Amsterdam, Plesmanlaan 121, 1066 CX, the Netherlands

   Department of Biometrics, Netherlands Cancer Institute –Antoni van Leeuwenhoek Amsterdam, Plesmanlaan 121, 1066 CX, the Netherlands

9. G. Veerman

   Erasmus MC · Erasmus MC Cancer Institute

   Affiliation as printed

   Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands

10. Stijn L.W. Koolen

    Erasmus MC · Erasmus MC Cancer Institute

    Affiliation as printed

    Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands; Department of Hospital Pharmacy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands

    Department of Hospital Pharmacy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands

    Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands

11. Harry J.M. Groen

    University Medical Center Groningen · University of Groningen

    Affiliation as printed

    Department of Pulmonary Diseases, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9713 GZ, the Netherlands

12. Anne‐Marie C. Dingemans

    Maastricht University Medical Centre · Erasmus MC · Maastricht University · Erasmus MC Cancer Institute

    Affiliation as printed

    Department of Pulmonary Diseases, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands; Department of Pulmonary Diseases, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands

    Department of Pulmonary Diseases, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands

    Department of Pulmonary Diseases, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands

13. Ron H.J. Mathijssen

    Erasmus MC · Erasmus MC Cancer Institute

    Affiliation as printed

    Department of Hospital Pharmacy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands

14. Egbert Frederik Smit Aachen Department of Pulmonary Diseases

    Leiden University · Leiden University Medical Center · The Netherlands Cancer Institute

    Affiliation as printed

    Department of Pulmonary Diseases, Netherlands Cancer Institute -Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Pulmonary Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, the Netherlands

    Department of Pulmonary Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, the Netherlands

    Department of Pulmonary Diseases, Netherlands Cancer Institute –Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands

15. Joachim G.J.V. Aerts corresponding

    Erasmus MC · Erasmus MC Cancer Institute

    Affiliation as printed

    Department of Pulmonary Diseases, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands. Electronic address: j.aerts@erasmusmc.nl

    Department of Pulmonary Diseases, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, the Netherlands