Durvalumab in frail and elderly patients with stage four non-small cell lung cancer: Study protocol of the randomized phase II DURATION trial

Jonas Kuon, Adriane Hommertgen, Johannes Krisam, Felix Lasitschka, Albrecht Stenzinger, Miriam Blasi, Farastuk Bozorgmehr, Martin Maenz, Meinhard Kieser, Marc Schneider, Michael Thomas, Jonas Kuon, Adriane Hommertgen, Johannes Krisam, Felix Lasitschka, Albrecht Stenzinger, Miriam Blasi, Farastuk Bozorgmehr, Martin Maenz, Meinhard Kieser, Marc Schneider, Michael Thomas

Abstract

Background: Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group.

Methods/design: This prospective, open label, treatment stratified, randomized phase II study will enroll 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be aged 70 years or older and/or "frail" (Charlson Comorbidity Index > 1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG > 1). Patients are stratified according to modified Cancer and Age Research Group (CARG) score: "fit" patients are allocated to combination CT (carboplatin/nab-paclitaxel) and "less fit" patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either four cycles of CT or two cycles of CT followed by two cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks. The primary endpoint is the rate of treatment-related grade III/IV adverse events (Common Terminology Criteria for Adverse Events (CTCAE) V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential "frail" and "elderly" patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers.

Discussion: The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients.

Trial registration: ClinicalTrials.gov, NCT03345810; initially registered on 17 November 2017. Eudra-CT, 2016-003963-20; initially registered on 3 January 2017.

Keywords: CARG; Durvalumab; Elderly; Frail; Lung cancer; PD-L1.

Conflict of interest statement

The DURATION trial received funding from AstraZeneca and Celgene. AstraZeneca and Celgene have not been involved in the study design and has no role in data collection, management, data analysis and interpretation, or in the decision to submit this protocol for publication.

All authors declare that they have no competing conflicts of interest.

Figures

Fig. 1
Fig. 1
DURATION patient allocation and treatment strategy

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