TY - JOUR T1 - RCT of first-line TKI <em>versus</em> intercalated TKI with chemotherapy for EGFR mutated NSCLC JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00239-2022 SP - 00239-2022 AU - Rolof G. P. Gijtenbeek AU - Vincent van der Noort AU - Joachim G. J. V. Aerts AU - Jeske A. Staal – van den Brekel AU - Egbert F. Smit AU - Frans H. Krouwels AU - Frank A. Wilschut AU - T. Jeroen N. Hiltermann AU - Wim Timens AU - Ed Schuuring AU - Joost D. J. Janssen AU - Martijn Goosens AU - Paul M. van den Berg AU - A. Joop de Langen AU - Jos A. Stigt AU - Ben E. E. M. van den Borne AU - Harry J. M. Groen AU - Wouter H. van Geffen AU - Anthonie J. van der Wekken Y1 - 2022/01/01 UR - http://openres.ersjournals.com/content/early/2022/06/30/23120541.00239-2022.abstract N2 - Introduction Previous studies have shown interference between EGFR TKI and chemotherapy in the cell cycle, thus reducing efficacy. In this RCT we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR mutated NSCLC.Materials and methods Treatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy (E). The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and toxicity.Results Between April 2014 to September 2016 twenty-two patients were randomized equally into both arms, the study was stopped due to slow accrual. Median follow up was 64 months. Median PFS was 13.7 months (95%CI 5.2–18.8) for CPE and 10.3 months (95%CI 7.1–15.5, HR 0.62 (95%CI 0.25–1.57)) for E, when compensating for number of days receiving erlotinib, PFS of CPE arm was superior (HR 0.24 (95% CI 0.07–0.83; p=0.02)). ORR was 64% for CPE versus 55% for E. Median OS was 31.7 months (95%CI 21.8–61.9) for CPE compared to 17.2 months (95%CI 11.5–45.5) for E (HR 0.58 (95%CI 0.22–1.41)). Patients treated with CPE had higher rates of treatment related fatigue, anorexia, weight loss and renal toxicity.Conclusion Intercalating erlotinib with cisplatin/pemetrexed provides a longer PFS compared to erlotinib alone in EGFR mutated NSCLC at the expense of more toxicity.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: RGP Gijtenbeek has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: Dr van der Noort has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: J.G.V.J. Aerts has received support for the present manuscript has been received from Roche, Lilly and Amgen. Consulting fees received from MSD, BMS, Boehringer Ingelheim, Amphera, Eli-Lilly, Takeda, Bayer, Roche, Astra Zeneca and BIOCAD, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from MSD, BMS, Boehringer Ingelheim, Amphera, Eli-Lilly, Takeda, Bayer, Roche, Astra Zeneca and BIOCAD, outside the submitted work. Patents planned, issued or pending; allogenic tumor cell lysate, Amphera, combination immunotherapy in cancer, and biomarker for immunotherapy, unrelated to this submission.Conflict of interest: A.J. Staal-van den Brekel has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: EF Smit has received support for the present manuscript has been received from Roche, Lilly and Amgen. Grants or contracts received from Boehringer Ingelheim, Bayer, Roche/Genentech, AstraZeneca and Bristol-Myers Squibb, outside the submitted work. Consulting fees received from Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol-Myers Squibb, Merck KGaA, MSD Oncology, Takeda, Bayer, Novartis, Daiichi Sankyo and Seattle Genetics, outside the submitted work.Conflict of interest: Frans Krouwels has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: Frank Wilschut has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: T. Jeroen. N. Hiltermann has received support for the present manuscript has been received from Roche, Lilly and Amgen. Grants or contracts received from Roche, BMS and Astra Zeneca, outside the submitted work. Consulting fees received from Roche, BMS, Astra Zeneca and MSD, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from BMS, outside the submitted work.Conflict of interest: Wim Timens has received support for the present manuscript has been received from Roche, Lilly and Amgen. Consulting fees received from Merck Sharp Dohme and Bristol-Myers-Squibb, outside the submitted work. Leadership or fiduciary role in other board, society, committee or advocacy group, outside the submitted work: Dutch Society of Pathology - Board member. Council for Research and Innovation of the Federation of Medical Specialists - memberConflict of interest: Ed Schuuring, PhD has received support for the present manuscript has been received from Roche, Lilly and Amgen. Grants or contracts received from Abbott, Biocartis, Astrazeneca, Invitae/Archer, Bayer, Bio-Rad, Roche, Agena Bioscience, CC Diagnostics and Boehringer Ingelheim, outside the submitted work. Consulting fees received from MSD/Merck, AstraZeneca, Roche, Novartis, Bayer, BMS, Lilly, Amgen, Illumina, Agena Bioscience, CC Diagnostics, Janssen Cilag (Johnson&amp;Johnson) and Astellas Pharma, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from Bio-Rad, Seracare, Roche, Biocartis, Lilly, Agena Bioscience and Illumina, outside the submitted work. Support for attending meetings and/or travel received from BioRad and Biocartis, outside the submitted work. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid Dutch Society of Pathology - Board member, unpaid. European Society of Pathology- Board member, unpaid. European Liquid Biopsy Society - Board member, unpaid.Conflict of interest: JDJ Janssen has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: M Goosens has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: PM van den Berg has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: Dr. de Langen reports grants from BMS, grants from MSD, grants from Boehringer, non-financial support from Merck Serono, grants from AstraZeneca, non-financial support from Roche, outside the submitted work.Conflict of interest: Jos A. Stigt has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: BEEM van den Borne has received support for the present manuscript has been received from Roche, Lilly and Amgen.Conflict of interest: Harry Groen has received support for the present manuscript has been received from Roche, Lilly and Amgen. Grants or contracts received from Roche and Boehringer Ingelheim, outside the submitted work. Consulting fees received from Lilly, Novartis, Roche / Genentech and AstraZeneca, outside the submitted work.Conflict of interest: WH van Geffen has received support for the present manuscript has been received from Roche, Lilly and Amgen. Leadership or fiduciary role in other board, society, committee or advocacy group for ERS and NVALT – unpaid, outside the submitted work. Other financial or non-financial interests outside the submitted work: Roche - Trial run by department. Amgen - Trial run by department.Conflict of interest: Dr. A.J. van der Wekken has received support for the present manuscript has been received from Roche, Lilly and Amgen. Grants or contracts received from Astra Zeneca, Pfizer, Boehringer-Ingelheim, Takeda and Roche, outside the submitted work. Consulting fees received from Astra Zeneca, Novartis, Boehringer-Ingelheim, Roche, Janssen, Pfizer, Lilly, Takeda and Merck, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from Pfizer, outside the submitted work. Support for attending meetings and/or travel received from Lilly, outside the submitted work. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for CPCT, outside the submitted work. ER -