LBA49 - Durvalumab after chemoradiotherapy in stage III NSCLC: 4-year survival update from the phase III PACIFIC trial

Background

In the phase III PACIFIC trial of patients (pts) with unresectable Stage III NSCLC without disease progression after concurrent chemoradiotherapy (cCRT), durvalumab significantly improved progression-free survival (PFS; stratified HR 0.52, 95% CI 0.42–0.65; P<0.0001; median 16.8 vs 5.6 months; data cutoff [DCO], 13 Feb 2017) and overall survival (OS; stratified HR 0.68, 95% CI 0.53–0.87; P=0.0025; median not reached vs 28.7 months; DCO, 22 Mar 2018) vs placebo (pbo), with manageable safety. We report updated, exploratory analyses of survival outcomes at 4 years, including the first estimate of median OS for the durvalumab arm.

Methods

Pts with WHO PS 0/1 (any tumour PD-L1 status) who had received ≥2 cycles of platinum-based cCRT (RT dosage typically 60–66 Gy in 30–33 fractions) were enrolled and randomised (2:1), 1–42 days post-cCRT, to IV durvalumab 10 mg/kg or pbo (q2w for ≤12 months), stratified by age, sex, and smoking history. Primary endpoints were PFS (blinded independent central review; RECIST v1.1) and OS (both measured from the time of randomisation). HRs and 95% CIs were estimated using a stratified log-rank test in the ITT population. Medians and OS/PFS rates at 48 months were estimated by Kaplan–Meier method.

Results

In total, 709/713 randomised patients received durvalumab (n/N=473/476) and pbo (n/N=236/237). The last pt had completed study treatment in May 2017, almost 3 years prior to the current DCO. As of 20 Mar 2020 (current DCO; median follow up, 34.2 months [range, 0.2–64.9]), updated PFS (stratified HR 0.55, 95% CI 0.44–0.67; median 17.2 vs 5.6 months) and OS (stratified HR 0.71, 95% CI 0.57–0.88) remained consistent with previous reports. Median OS for the durvalumab arm was determined for the first time: 47.5 months (pbo, 29.1 months). The 48-month OS rates were 49.6% vs 36.3% for durvalumab vs pbo, and PFS rates were 35.3% vs 19.5% respectively. Updates to treatment effects for pt subgroups will be reported.

Conclusions

These updated analyses of PFS and OS demonstrate durable benefit with durvalumab after cCRT. Approximately half of patients randomised to durvalumab in PACIFIC remain alive at 4 years, and about a third remain both alive and progression free, almost 3 years after the last pt completed study treatment.

Clinical trial identification

NCT02125461.

Editorial acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Aaron Korpal, PhD, of Cirrus Communications (Manchester, UK), an Ashfield company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

C. Faivre-Finn: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution), Travel/Accommodation/Expenses: Elekta. D. Vicente: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Roche. T. Kurata: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): Ono; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Takeda. D. Planchard: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: prIME Oncology; Advisory/Consultancy: Peer CME; Advisory/Consultancy: Roche; Advisory/Consultancy: Samsung. L. Paz-Ares: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Angem; Advisory/Consultancy: Incyte; Advisory/Consultancy: Takeda; Advisory/Consultancy: Blueprint; Advisory/Consultancy: Bayer; Leadership role: Altum Sequencing; Leadership role: Genomica; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Ipsen. J.F. Vansteenkiste: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Bristol-Myers Squibb. D.R. Spigel: Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Aeglea Biotherapeutics; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Bind Therapeutics; Honoraria (institution), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (institution), Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Celldex Therapeutics; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Eli Lilly; Honoraria (institution), Research grant/Funding (institution): EMD Serono; Honoraria (institution), Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): G1 Therapeutics; Honoraria (institution), Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Grail; Research grant/Funding (institution): ImClone Systems; Honoraria (institution), Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Nektar Therapeutics; Research grant/Funding (institution): Neon Therapeutics; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Takeda Pharmaceuticals; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Transgene; Research grant/Funding (institution): UT Southwestern; Research grant/Funding (institution): Cyteir Therapeutics; Research grant/Funding (institution): Apollomics; Research grant/Funding (institution): Elevation Oncology; Honoraria (institution): Aptitude Health; Honoraria (institution): Bayer; Honoraria (institution): Dracen Pharmaceuticals; Honoraria (institution): Exelixis; Honoraria (institution): Iksuda Therapeutics; Honoraria (institution): Intellisphere; Honoraria (institution): Jazz Pharmaceuticals; Honoraria (institution): Mirati Therapeutics; Honoraria (institution): Molecular Templates; Honoraria (institution): Puma Biotechnology. M.C. Garassino: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Non-remunerated activity/ies: Eli Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Otsuka Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): 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 (institution): Tiziana Sciences; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: MSD; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline S.p.A.; Advisory/Consultancy: Sanofi-Aventis; Advisory/Consultancy, Research grant/Funding (institution): Spectrum Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicine; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): United Therapeutics Corporation; Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy: Janssen. M. Reck: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Samsung. S. Senan: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): ViewRay Inc.; Honoraria (self): Celgene; Honoraria (self): MSD; Honoraria (self), Research grant/Funding (institution): Varian Medical Systems. J. Naidoo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Research grant/Funding (institution): Merck. A. Rimner: Research grant/Funding (institution): Varian Medical Systems; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Merck; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Pfizer; Honoraria (self): Research to Practice; Honoraria (self): Cybrexa; Honoraria (self): More Health; Non-remunerated activity/ies: Philips/Elektra. Y-L. Wu: Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Speaker Bureau/Expert testimony: Sanofi. J.E. Gray: Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Boehringer Ingelheim. M. Özgüroğlu: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas; Honoraria (self): Novartis; Honoraria (self): Roche; Travel/Accommodation/Expenses: Bristol-Myers Squibb. K.H. Lee: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer. M. Newton: Full/Part-time employment: AstraZeneca. L. Wang: Full/Part-time employment: AstraZeneca. P. Thiyagarajah: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. S.J. Antonia: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: CBMG; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Memgen; Advisory/Consultancy, Travel/Accommodation/Expenses: RAPT; Advisory/Consultancy: Venn; Advisory/Consultancy, Travel/Accommodation/Expenses: Achilles Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses: Celsius; Advisory/Consultancy: Samyang Biopharma; Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution): Novartis.