Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer

Abstract

PURPOSE The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non–small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned. METHODS Patients with WHO performance status 0 or 1 (any tumor programmed cell death-ligand 1 status) were randomly assigned (2:1) to durvalumab (10 mg/kg intravenously; administered once every 2 weeks for 12 months) or placebo, stratified by age, sex, and smoking history. Time-to-event end point analyses were performed using stratified log-rank tests. Medians and landmark survival rates were estimated using the Kaplan-Meier method. RESULTS Seven hundred and nine of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237). As of January 11, 2021 (median follow-up, 34.2 months [all patients]; 61.6 months [censored patients]), updated OS (stratified HR, 0.72; 95% CI, 0.59 to 0.89; median, 47.5 v 29.1 months) and PFS (stratified HR, 0.55; 95% CI, 0.45 to 0.68; median, 16.9 v 5.6 months) remained consistent with the primary analyses. Estimated 5-year rates (95% CI) for durvalumab and placebo were 42.9% (38.2 to 47.4) versus 33.4% (27.3 to 39.6) for OS and 33.1% (28.0 to 38.2) versus 19.0% (13.6 to 25.2) for PFS. CONCLUSION These updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.

Chemoradiation followed by adjuvant durvalumab in stage III non–small cell lung cancer: Real‐world comparison of treatment outcomes to historical controls treated with chemoradiation alone

“…The results of this single institution retrospective analysis demonstrate that for patients with locally advanced stage III NSCLC, the use of adjuvant durvalumab after completion of chemoradiation improves PFS and OS compared to historic controls treated with chemoradiation alone. Although most patients in our trial did not conform to eligibility criteria for inclusion in the PACIFIC trial because of delay in starting adjuvant durvalumab ( n = 51), history of immune disease ( n = 3), or ECOG status ≥2 ( n = 4), the improved PFS and OS with adjuvant durvalumab observed in our study are consistent with outcomes reported in the PACIFIC trial and other real‐world studies 7–18 . The real‐world data presented in this study, although limited, suggest that future clinical trials consider inclusion of patients who begin durvalumab therapy beyond 42 days after completion of chemoradiation, have a prior history of immune disease, or have an ECOG performance status ≥2.…”

“…The use of immunotherapy in patients with stage IV NSCLC is associated with improved overall survival (OS) and progression free survival (PFS) 6 . The PACIFIC trial reported improved outcomes in carefully selected patients with unresectable stage III NSCLC treated with 1 year of adjuvant durvalumab following chemoradiation compared to a control group treated with chemoradiation followed by placebo 7–11 . Subsequent reports from real‐world single and multicenter studies confirmed the improved OS and PFS reported in the PACIFIC trial 12–18 .…”

Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN

“…After more than three decades of limited progress in treating extensive-stage small-cell lung cancer (ES-SCLC), the introduction of immune checkpoint inhibitors, particularly the programmed death ligand-1 (PD-L1) inhibitors durvalumab and atezolizumab, has provided significant improvements in overall survival (OS). 1 , 2 Immune checkpoint inhibitors have shown impressive durable survival benefit in non-small-cell lung cancer; 3 , 4 , 5 however, as immunotherapy trials in ES-SCLC are comparatively recent, the extent to which long-term survival can be improved in this setting is not yet established.…”

COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non–Small-Cell Lung Cancer

“…4-6 Furthermore, recent 5-year data from PACIFIC demonstrated robust and sustained OS benefit plus durable PFS with durvalumab, with 5-year OS and PFS rates of 42.9% and 33.1%, respectively. 7…”

“…AFFILIATIONS 1 Yale Cancer Center, New Haven, CT 2 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain 3 Gustave Roussy, Villejuif, France 4 Institut Catal à d'Oncologia, Badalona-Hospital Germans Trias i Pujol, Barcelona, Spain 5 Cross Cancer Institute, Edmonton, AB, Canada 6 Centre Hospitalier Intercommunal de Cr éteil, Cr éteil, France 7 Consorcio Hospitalario Provincial de Castell ón, Castell ón, Spain 8 Cancer Center of Kansas, Wichita, KS 9 University of Colorado Anschutz Medical Campus, Aurora, CO 10 AstraZeneca, Cambridge, United Kingdom 11 AstraZeneca, Gaithersburg, MD 12 Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 13…”