LBA1 - Durvalumab in combination with chemoradiotherapy for patients with unresectable stage III NSCLC: Final results from PACIFIC-2

Background

The PACIFIC trial established consolidation durvalumab (D) after chemoradiotherapy (CRT) as SoC for pts with unresectable stage III NSCLC. However, up to 30% of pts are ineligible due to progression during/shortly after CRT or inadequate recovery from CRT-related toxicity. The phase III PACIFIC-2 trial evaluated D initiated concurrently with platinum-based concurrent CRT (cCRT) followed by consolidation D, compared with cCRT alone, in pts with unresectable stage III NSCLC.

Methods

PACIFIC-2 (NCT03519971) was a randomized double-blind study. Treatment (Tx)-naïve pts with WHO PS 0/1 and histologically/cytologically confirmed stage III NSCLC were randomized (2:1) to receive SoC cCRT concurrently with D or placebo (PBO) IV Q4W, stratified by age and disease stage. Pts then received consolidation D/PBO until progression, unacceptable toxicity, consent withdrawal, or other discontinuation criteria. The primary endpoint was PFS (BICR; RECIST v1.1).

Results

327/328 randomized pts received Tx (D arm, n=219; PBO arm, n=108). A higher % of pts in the D vs PBO arm had T4 tumors (57.5% vs 48.6%) and squamous histology (55.3% vs 47.7%). As of 7 Sep 2023 (data cutoff), median follow-up in all (censored) pts was 30.5 (55.5) months. There was a trend (not statistically significant) toward improved PFS with D vs PBO (HR, 0.85; 95% CI: 0.65–1.12; P=0.247); median PFS was 13.8 vs 9.4 months. There was no significant difference in OS (HR, 1.03; 95% CI: 0.78–1.39; P=0.823); median OS was 36.4 vs 29.5 months. Max grade 3/4 any-cause AEs occurred in 53.4% vs 59.3% with D vs PBO; 25.6% vs 12.0% had AEs that led to discontinuation of D/PBO (14.2% vs 5.6% in the first 4 months); 47.0% vs 51.9% had serious AEs; and 13.7% vs 10.2% had AEs with outcome of death. Pneumonitis/radiation pneumonitis occurred in 28.8% vs 28.7%.

Conclusions

In PACIFIC-2, concurrent D and CRT did not improve outcomes vs CRT alone. Overall, safety and tolerability were consistent with the known profiles for D and CRT, although one quarter of pts had AEs leading to discontinuation of D, the majority of which occurred in the first 4 months. Consolidation D remains SoC for pts with unresectable stage III NSCLC who do not progress on definitive CRT.

Clinical trial identification

NCT03519971 (release date: May 9, 2018).

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Andrew Gannon of Ashfield MedComms (New York, NY, USA), an Inizio company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

J.D. Bradley: Non-Financial Interests, Personal, Advisory Board: Varian Medical Systems, Inc, Mevion Medical Systems, AstraZeneca, Inc, Genentech, Inc; Financial Interests, Institutional, Research Grant: Varian Medical Systems, Inc; Non-Financial Interests, Institutional, Principal Investigator: PACIFIC 2 with AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: FLASH RT Spinal Cord Toxicity in a minipig model with Varian. S. Sugawara: Financial Interests, Personal, Speaker’s Bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Kyowa Kirin, Lilly, Merck, Merck Sharp & Dohme K.K., Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical Co., Ltd., Otsuka, Pfizer, Taiho Pharmaceutical Co., Ltd., Takeda, Thermo Fisher Scientific, Towa Pharmaceutical, Sysmex Corp., Eisai Co., Ltd.; Financial Interests, Institutional, Principal Investigator: AnHeart, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Merck Sharp & Dohme K.K., Nippon Boehringer Ingelheim., Ono Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Principal Investigator: AbbVie, Amgen, Taiho Pharmaceutical Co., Ltd., Takeda, Accerise, Parexel International Inc.. K.H.H. Lee: Non-Financial Interests, Personal, Advisory Board: BMS, Eli Lilly, AstraZeneca, Merck, MSD, Yuhan, Pfizer; Non-Financial Interests, Personal and Institutional, Funding: Merck. A. Demirkazik: Non-Financial Interests, Personal, Principal Investigator: AstraZeneca. V. Sriuranpong: Financial Interests, Personal, Other, Honoraria: Novartis, AstraZeneca, Roche, Pfizer, MSD Oncology, Amgen, Takeda, Eisai; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Roche, Amgen, MSD Oncology, Astellas Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, MSD Oncology, Takeda, Amgen; Financial Interests, Personal, Other, Travel, accommodations, expenses: Eisai, Roche, AstraZeneca. A. Gelatti: Financial Interests, Personal, Invited Speaker: Roche, MSD, BMS, AstraZeneca, Pfizer, Boehringer-Ingelheim, Bayer, Lilly, Novartis, Amgen, Takeda, Novartis, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Advisory Board: MSD, Roche, BMS, Boehringer Ingelheim, AstraZeneca, Amgen, Bayer, Lilly, Novartis, Takeda, Beigene, Daiichi Sankyo, Pfizer, Sanofi; Financial Interests, Personal, Member of Board of Directors: AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Principal Investigator: MSD, BMS, AstraZeneca, Roche, IRxs, Janssen, Lilly, GSK, Novartis, Daiichi Sankyo, Gilead, Beigene, Boehringer Ingelheim, Amgen. J. Menezes: Financial Interests, Personal, Invited Speaker: BMS; Non-Financial Interests, Personal, Principal Investigator: BMS, AstraZeneca, MSD. B. Zurawski: Financial Interests, Personal, Other: Honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, GSK, Janssen-Cilag, MSD, and Roche. M. Newton, P. Chander: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N. Jia: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. Z.F. Bałdyga-Bielecka: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. All other authors have declared no conflicts of interest.