In the ph III PACIFIC trial, durvalumab after concurrent chemoradiotherapy (cCRT) significantly improved survival outcomes in pts with Stage III, unresectable NSCLC with manageable safety. As many pts are ineligible for cCRT, we aimed to assess durvalumab after sequential (s)CRT in pts with Stage III, unresectable NSCLC in the ph II PACIFIC-6 trial (NCT03693300).
Up to 120 pts with ECOG PS ≤2 and no progression after sCRT will receive durvalumab 1500 mg IV q4w ≤24 months or until progression, unacceptable toxicity or consent withdrawal. The primary endpoint is assessment of safety/tolerability, defined by gr 3/4 treatment-related AEs occurring within 6 months. Pre-specified early assessment was planned after ≥50 pts in a PS 0/1 cohort (∼100–120 expected) had received durvalumab ≥6 months.
As of August 24, 2020, 50 pts with ECOG PS 0/1 (46%/54%) had received durvalumab for a median 24.0 weeks. Median age was 67.0 years; 64% were male; 64% had adenocarcinoma histology; 38%/52%/10% had Stage IIIA/B/C disease; and 48%/52% had PD-L1 tumor cell expression ≥/< 1%. Many pts had past/present medical conditions, including vascular (62%), metabolism (54%) and respiratory (50%) disorders. Pts had received a median 4 CT cycles, with 68% receiving a total RT dose of ≥54 to ≤60 Gy and 32% receiving >60 to ≤66 Gy. In most pts (84%), CT and RT did not overlap. Best response to prior sCRT (RECIST 1.1) included PR (74%) and SD (18%). In all, 88% had any AEs and 12% had gr 3/4 AEs; 70% had any possibly related AEs (PRAEs) and 4% had gr 3/4 PRAEs (including 2% with the gr 3/4 PRAE pneumonitis). 22% had SAEs (10% PRSAEs) and 2 pts had fatal AEs (1 pt fatal PRAE). 72% had AESIs, including pneumonitis (32%) and dermatitis/rash (28%). 9/25 pts who discontinued did so due to AEs, most commonly pneumonitis (n = 8).
Based on early assessment, durvalumab after sCRT appears to have a similar safety profile to that with durvalumab after cCRT in PACIFIC pts with Stage III, unresectable NSCLC. Full cohort results for safety primary analysis in the near future are awaited.
NCT03693300.
Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca.
AstraZeneca.
AstraZeneca.
M.C. Garassino: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), PI, MISP in Thimic malignancies; Speaker, advisory board: Eli Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Local PI, Enrollment in clinical Trials in NSCLC; Speaker;advisory board: Otsuka Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), PI, Enrollment and Steering Committee in clinical Trials in NSCLC; Consulting, advisory boards, lectures; steering committee: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC; advisory board: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC; Speaker, advisory board: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC; Speaker, advisory board: Roche; Advisory/Consultancy, Research grant/Funding (self), PI, MISP MISP Sunitinib in thymic malignancies; advisory board: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC; Speaker, advisory board: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Inivata; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Research grant/Funding (self), PI, Enrollment in clinical Trials Thimic malignancies: Tiziana Sciences; Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC: Clovis; Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC: Merck Serono; Advisory/Consultancy, Research grant/Funding (self), PI, Enrollment in clinical Trials in Mesothelioma; advisory board: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC; consulting, advisory boards, lectures; steering committee: MSD; Advisory/Consultancy, Research grant/Funding (self), Local PI, Enrollment and Steering committee in clinical Trials in NSCLC; advisory board: GlaxoSmithKline S.p.A.; Advisory/Consultancy, Research grant/Funding (self), Advisory board; PI, Enrollment in clinical Trials: Sanofi-Aventis; Advisory/Consultancy, Research grant/Funding (self), PI, Enrollment in clinical Trials; Advisory board; steering committee: Spectrum Pharmaceutcials; Advisory/Consultancy, Research grant/Funding (self), PI, Enrollment in clinical Trials; Advisory board; steering committee: Blueprint Medicine; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy, Research grant/Funding (self): Janssen; Non-remunerated activity/ies, Principal Investigator Keynote 189;MISP pembrolizumab in low expressors PD-L1(J. Mazieres: Advisory/Consultancy: Merck; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Hengrui; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Boehringer; Advisory/Consultancy, Research grant/Funding (self): Pierre Fabre. M. Reck: Honoraria (self), Honoraria for lectures and consultancy: Amgen; Honoraria (self), Honoraria for lectures and consultancy: AstraZeneca; Honoraria (self), Honoraria for lectures and consultancy: BMS; Honoraria (self), Honoraria for lectures and consultancy: Boehringer Ingelheim; Honoraria (self), Honoraria for lectures and consultancy: Lilly; Honoraria (self), Honoraria for lectures and consultancy: Merck; Honoraria (self), Honoraria for lectures and consultancy: MSD; Honoraria (self), Honoraria for lectures and consultancy: Novartis; Honoraria (self), Honoraria for lectures and consultancy: Pfizer; Honoraria (self), Honoraria for lectures and consultancy: Roche; Honoraria (self), Honoraria for lectures and consultancy: Samsung. R. Bernabe: Research grant/Funding (institution): Roche. I. Diaz Perez: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. W. Sawyer: Full/Part-time employment, Contractor: AstraZeneca. N. Trunova: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. C. Faivre-Finn: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (self), Travel/Accommodation/Expenses: Elekta. All other authors have declared no conflicts of interest.