Protocol for a phase II randomised controlled trial of TKI alone versus TKI and local consolidative radiation therapy in patients with oncogene driver-mutated oligometastatic non-small cell lung cancer

Anil Tibdewal, JaiPrakash Agarwal, Naveen Mummudi, Vanita Noronha, Kumar Prabhash, Vijay Patil, Nilendu Purandare, Amit Janu, Rajiv Kaushal, Sadhna Kannan, Anil Tibdewal, JaiPrakash Agarwal, Naveen Mummudi, Vanita Noronha, Kumar Prabhash, Vijay Patil, Nilendu Purandare, Amit Janu, Rajiv Kaushal, Sadhna Kannan

Abstract

Introduction: Tyrosine kinase inhibitors (TKIs) have significantly improved the progression-free survival (PFS) of metastatic non-small cell lung cancer (NSCLC) with oncogene mutations of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) compared with systemic therapy alone. However, the majority eventually develop resistance with a median PFS of 8-12 months. The pattern of failure studies showed disease relapse at the original sites of the disease-harbouring resistant tumour cells.

Methods and analysis: This study is designed as a phase II randomised controlled trial to evaluate the efficacy of local consolidative radiation therapy (LCRT) in addition to TKI in upfront oligometastatic NSCLC. Patients will be screened at presentation for oligometastases (≤5 sites) and will start on TKI after confirmation of EGFR or ALK mutation status. After initial TKI for 2-4 months, eligible patients will be randomised in a 1:1 ratio with stratification of oligometastatic sites (1-3 vs 4-5), performance status of 0-1 versus 2 and brain metastases. The standard arm will continue to receive TKI, and the intervention arm will receive TKI plus LCRT. Stereotactic body radiation therapy will be delivered to all the oligometastatic sites.The primary end point is PFS, and secondary end points are overall survival, local control of oligometastatic sites, toxicity and patient-reported outcomes. The sample size calculation took a median PFS of 10 months in the standard arm. To detect an absolute improvement of 7 months in the interventional arm, with a one-sided alpha of 5% and 80% power, a total of 106 patients will be accrued over a period of 48 months.

Ethics and dissemination: The study is approved by the Institutional Ethics Committee II of Tata Memorial Centre, Mumbai, and registered with Clinical Trials Registry-India, CTRI/2019/11/021872, dated 5 November 2019. All eligible participants will be provided with a participant information sheet and will be required to provide written informed consent for participation in the study. The study results will be presented at a national/international conference and will be published in a peer-reviewed journal.

Keywords: chemotherapy; oncology; radiotherapy; thoracic medicine.

Conflict of interest statement

Competing interests: VN has received institutional research funding from Amgen, Sanofi India, Dr. Reddy’s Laboratories, Intas Pharmaceuticals and Astra Zeneca Pharma India. All research grants have been paid to the institution. KP has received research funding from Dr. Reddy’s Laboratories, Fresenius Kabi India, Alkem Laboratories, Natco Pharma, BDR Pharmaceuticals and Roche Holding AG (all research grants paid to the institution and are unrelated to this study project).

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study schema. ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; LCRT, local consolidative radiation therapy; NSCLC, non-small cell lung cancer; OM, oligometastases; PFS, progression-free survival; PS, performance status.

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