66MO - Durvalumab after radiotherapy (RT) in patients (pts) with unresectable Stage III NSCLC ineligible for chemotherapy (CT): final analysis of the phase 2 DUART study

Background

Currently, pts with unresectable Stage III NSCLC ineligible for CT receive RT alone, with unsatisfactory outcomes. Results from an interim analysis of DUART (NCT04249362) showed that RT followed by durvalumab was well tolerated in this older, frailer population. Importantly, preliminary efficacy data were encouraging. Here we report the final analysis, including updated PFS and OS after longer follow-up.

Methods

Pts deemed ineligible for CT with no progression after RT were enrolled into two parallel cohorts by prior RT dose (A: definitive RT, 60 Gy ± 10% or bioequivalent dose [BED]; B: palliative RT, 40 to <54 Gy or BED). Pts received durvalumab 1500 mg IV Q4W for 12 mo or until progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was safety/tolerability; specifically, incidence of grade 3/4 possibly-related adverse events (PRAEs) occurring within 6 mo of first dose.

Results

At the final analysis data cutoff, median total treatment duration was 36.0 wk. Incidence of grade 3/4 PRAEs within 6 mo of first dose remained unchanged from the interim analysis (9.8%). Key updated PFS and OS data are summarized in the Table. In both cohorts, PFS and OS appeared longer in pts with PD-L1 tumor cell expression ≥1% vs <1% (data will be presented). Updated confirmed objective response rates (ORRs) in the definitive and palliative RT cohorts were 34.0% (95% CI: 21.5–48.3) and 24.5% (95% CI: 13.3–38.9). Additional results will be presented. Table: 66MO

Data cutoff: Dec 6, 2023 (median [range] follow-up in censored pts: PFS, 11.1 mo [0.0–33.2]; OS, 16.4 mo [0.9–33.4]).^aEstimated by Kaplan–Meier method.CI, confidence interval; NC, not calculable; OS, overall survival; PFS, progression-free survival.

Conclusions

Compared with historical data for RT alone, promising OS and PFS outcomes were observed with durvalumab after RT across both cohorts. ORR was higher and median PFS and OS were longer in the definitive RT cohort. The efficacy and safety data from DUART suggest that durvalumab following definitive or palliative RT may be a potential treatment option in a frailer and older population ineligible for CT.

Clinical trial identification

NCT04249362 (release date: January 30, 2020).

Editorial acknowledgement

Medical writing support for this abstract, under the direction of the authors, was provided by James Holland (Macclesfield, UK) of Ashfield MedComms, an Inizio company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

A.R. Filippi: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Role: Radiomics (OncoRadiomics); Other, Personal, Coordinating PI: AstraZeneca; Other, Institutional, Funding: AstraZeneca, Roche, MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Institutional, Local PI: AstraZeneca, Roche, MSD; Non-Financial Interests, Personal, Membership or affiliation: ESMO, ESTRO, IASLC; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Takeda; Other, Personal, Steering Committee Member: AstraZeneca, EORTC. M.R. Garcia-Campelo: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, F. Hoffmann-La Roche, Janssen, Lilly, MSD, Pfizer, Sanofi, Takeda, Pfizer; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, F. Hoffmann-La Roche, GSK, Janssen, Lilly, Merck, Mirati Therapeutics, MSD, Novartis, Amgen, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, F. Hoffmann-La Roche, GSK, Janssen, Lilly, Merck, Mirati Therapeutics, MSD, Novartis, Amgen, Pfizer . J. Paoli: Non-Financial Interests, Personal, Research Funding: AZ, BMS, MSD, Pfizer. D.M. Kowalski: Financial Interests, Personal, Advisory Board: MSD, BMS, Roche, Pfizer, Takeda, Johnson&Johnson, AstraZeneca, Medison, Amgen; Financial Interests, Personal, Advisory Role: MSD, BMS, Roche, Pfizer, Takeda, Johnson & Johnson, AstraZeneca, Medison, Amgen; Financial Interests, Personal, Local PI: MSD, BMS, Roche, Pfizer, Takeda, Johnson&Johnson, AstraZeneca. C. Bennati: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Pfizer, Janssen; Financial Interests, Personal, Advisory Role: Daiichi Sankyo. P. Borghetti: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Takeda; Other, Personal and Institutional, Principal Investigator: AstraZeneca, Roche, MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Roche; Non-Financial Interests, Personal, Steering Committee Member: AstraZeneca. D.L. Cortinovis: Financial Interests, Personal, Advisory Role: MSD, BMS, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Amgen, Takeda, Beigene, Janssen, Pfizer; Financial Interests, Personal, Speaker’s Bureau: MSD, BMS, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Amgen, Takeda, Beigene, Jannsen, Pfizer. A. Delmonte: Financial Interests, Personal, Advisory Board: Novartis, Takeda. C. Genova: Other, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Novartis; Other, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Novartis; Other, Institutional, Local PI: AstraZeneca, BMS, MSD, Roche, Novartis. R.M. Mroz: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal, Ownership Interest, Centrum Medycyny Oddechowej Mroz Spolka jawna: AstraZeneca, MSD, BMS, Roche. G. Tonini: Financial Interests, Personal, Advisory Board: Molteni, Novartis, MSD, PharmaMar. G. Wetherill: Financial Interests, Personal, Financially compensated role, Consultant statistician: AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant statistician: AstraZeneca. I. Diaz Perez: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N.E. Georgoulia: Financial Interests, Personal, Financially compensated role: AstraZeneca; Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R. Dziadziuszko: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, BMS, Novartis, Amgen, Regeneron; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, Takeda, MSD, Novartis, Amgen, Regeneron, Pfizer; Financial Interests, Personal, Principal Investigator: AstraZeneca, Amgen, Roche, Ryvu Therapeutics, Takeda, MSD, Novartis, ThurningPoint Therapeutics, Pfizer; Financial Interests, Personal, Product Samples: Novartis, Pfizer. All other authors have declared no conflicts of interest.