LBA6 - PACIFIC-5: A phase III study of consolidation durvalumab (D) in patients (pts) with unresectable stage III NSCLC and no progression after concurrent or sequential chemoradiotherapy (cCRT or sCRT)

Background

PACIFIC established consolidation D after cCRT as standard of care for pts with unresectable Stage III NSCLC, but many pts receive sCRT in practice. We present progression-free survival (PFS; final analysis) and overall survival (OS; interim analysis) from PACIFIC-5 (NCT03706690), a randomized, double-blind trial of consolidation D in a broader, largely Asian population.

Methods

Pts with unresectable Stage III NSCLC and no progression after definitive, platinum-based cCRT or sCRT were randomized 2:1, stratified by tumor cell PD-L1 expression (<1% vs ≥1%) and prior treatment (Tx; cCRT vs sCRT), to receive D 1500 mg IV Q4W or placebo (PBO) until progression, toxicity, or consent withdrawal. The primary endpoint was PFS by blinded independent central review (RECIST v1.1). OS (key) and safety were secondary endpoints. Efficacy analyses used the modified intent-to-treat population (mITT), which excluded pts with sensitizing EGFR/ALK aberrations. Safety analyses included all pts receiving ≥1 dose of D or PBO.

Results

379/381 pts in the mITT received Tx (D, n=251/252; PBO, n=128/129). Baseline characteristics were generally balanced, though more pts in the D vs PBO arm had ECOG PS 1 (68.3% vs 55.0%) and Stage IIIC disease (23.4% vs 14.7%); pts were Asian (71.9%) or White (28.1%). At data cutoff (23 June 2024), median follow-up (all pts) was 28.9 mo. PFS was significantly improved with D vs PBO (HR 0.75; 95% CI: 0.58–0.99; P=0.038); median PFS (95% CI) was 14.0 (10.9–18.0) vs 6.5 (5.4–13.8) mo. Subgroup analyses suggested consistent PFS benefit after cCRT (HR 0.76; 95% CI: 0.55–1.06) or sCRT (HR 0.75; 95% CI: 0.49–1.18). There was a favorable trend in OS with D vs PBO (HR 0.87; 95% CI: 0.66–1.17; P=0.346). In the safety set (D, n=271; PBO, n=134), max Grade 3/4 any-cause AEs occurred in 26.9% vs 23.9% of pts with D vs PBO; AEs led to Tx discontinuation in 14.4% vs 8.2%; 1.5% vs 0% had Tx-related fatal AEs; and pneumonitis or radiation pneumonitis occurred in 39.5% vs 40.3%.

Conclusions

PACIFIC-5, the first international phase 3 study of D in this setting in a predominantly Asian population, met its primary endpoint of improved PFS after either cCRT or sCRT. OS follow-up is ongoing.

Clinical trial identification

NCT03706690; first posted 16 October 2018; last update posted 07 August 2024.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Eric Exner, MD, PhD, of Ashfield MedComms (New York, NY, USA), an Inizio company.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

Y. Wu: Financial Interests, Personal, Coordinating PI: AstraZeneca, Roche, Pfizer; Financial Interests, Personal, Invited Speaker, Speaker fees: AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Merck Sharp & Dohme, Pfizer, Roche, Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Hengrui, Roche; Financial Interests, Personal, Steering Committee Member, Honoraria: AstraZeneca, Pfizer, Roche. Y. Pan: Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BMS, MSD, Pfizer, and Roche. M. Krzakowski: Financial Interests, Personal, Advisory Board: Roche, MSD, BMS, AstraZeneca, Takeda; Financial Interests, Personal, Advisory Role: Roche, MSD, BMS, AstraZeneca, Takeda; Financial Interests, Personal, Coordinating PI: Roche, MSD, BMS, AstraZeneca, Takeda; Financial Interests, Personal, Invited Speaker: Roche, MSD, BMS, AstraZeneca, Takeda; Financial Interests, Personal, Local PI: Roche, MSD, BMS, AstraZeneca, Takeda; Financial Interests, Personal, Principal Investigator: Roche, MSD, BMS, AstraZeneca, Takeda; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, MSD, BMS, AstraZeneca, Takeda. M.A.N. Sendur: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, Astellas, BMS, MSD, Lilly, Gilead, Takeda, Janssen; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Novartis, Astellas, BMS, MSD, Lilly, Gilead, Takeda, Janssen. Y. Kim: Financial Interests, Personal, Research Grant: AstraZeneca; Non-Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Takeda, Yuhan; Financial Interests, Personal, Steering Committee Member: Yuhan. Y. Yang: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca. R. Mao, B. Zhang: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. All other authors have declared no conflicts of interest.