LBA61 - Durvalumab (durva) after sequential chemoradiotherapy (CRT) in patients (pts) with unresectable stage III NSCLC: Final analysis from PACIFIC-6

Background

In the phase 3, placebo-controlled PACIFIC trial, durva after concurrent CRT (cCRT) significantly improved survival in pts with unresectable Stage III NSCLC, with manageable safety. As many pts are considered unsuitable for cCRT, the phase 2 PACIFIC-6 trial (NCT03693300) assessed safety and efficacy with durva after sequential CRT (sCRT); interim data indicated this approach had a similar safety profile to that with durva after cCRT in PACIFIC with encouraging preliminary efficacy. We report the final analysis from PACIFIC-6.

Methods

Pts with unresectable Stage III NSCLC, ECOG performance status (PS) ≤2, and no progression after platinum-based sCRT were enrolled to receive durva 1500 mg IV, every 4 wk for up to 24 mo, or until progression, unacceptable toxicity, or consent withdrawal. The primary endpoint (reported previously) was the incidence of grade 3/4 possibly related AEs (PRAEs) occurring within 6 mo. Secondary endpoints included OS and PFS (investigator-assessed; RECIST v1.1), analysed by Kaplan–Meier method.

Results

As of Mar 20, 2023, 117 pts were enrolled. Most had PS 1/2 (59.8%; PS 1, n=67; PS 2, n=3), were aged ≥65 yr (65.8%; age range: 39–85 yr), and had stage IIIB/IIIC NSCLC (63.2%). Nearly all had past/present comorbidities (98.3%), mostly vascular (59.0%), respiratory (53.0%) and metabolic (51.3%) disorders. Median treatment duration was 41.0 wk (range: 4–108). Overall, 4.3% (95% CI: 1.4–9.7) of pts had grade 3/4 PRAEs within 6 mo, and 6.0% had grade 3/4 PRAEs during the entire study period (1 pt had a PRAE with outcome of death). Pneumonitis was the most frequently reported PRAE of any grade (17.1%) and grade 3/4 (1.7%). 27.4% of pts discontinued durva due to AEs of any cause. Median duration of follow-up among pts censored for OS was 32.6 mo (range: 4.4–45.7). Median OS was 39.0 mo (95% CI: 30.6–not calculable), the 3-yr OS rate was 56.5% (95% CI: 46.4–65.5), and median PFS was 13.1 mo (95% CI: 7.4–19.9).

Conclusions

Durva after sCRT maintained a similar safety profile to that seen with durva after cCRT in PACIFIC and demonstrated encouraging efficacy in a frailer population, supporting use of this approach for pts who are considered unsuitable for cCRT.

Clinical trial identification

NCT03693300 (release date: October 02, 2018).

Editorial acknowledgement

Medical writing support for this abstract, under the direction of the authors, was provided by Werner Gerber, PhD, and Aaron Korpal, PhD, of Ashfield MedComms (Macclesfield, UK), an Inizio Company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M.C. Garassino: Financial Interests, Personal, Other, Honoraria: MSD Oncology, AstraZeneca/MedImmune, GSK, Takeda, Roche, Bristol-Myers Squibb, Daiichi Sankyo/AstraZeneca, Regeneron, Pfizer, Blueprint Pharmaceutic, Novartis, Sanofi/Aventis; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb, MSD, AstraZeneca, Novartis, Takeda, Roche, Sanofi-Aventis, Celgene, Daiiki Sankyo, Pfizer, Seattle Genetics, Eli Lilly, GSK, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, Janssen, Regeneron, Bayer, AbbVie, Mirati, Merck, Boheringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD Oncology, Merck, Mirati, Daiichi Sankyo/AstraZeneca; Financial Interests, Institutional, Research Funding: Bristol-Myers Squibb, MSD, Roche/Genentech, AstraZeneca/MedImmune, AstraZeneca, Pfizer, GSK, Novartis, Merck, Incyte, Takeda, Spectrum Pharmaceuticals, Blueprint Medicines, Eli Lilly, AstraZeneca, Ipsen, Janssen, Exelixis, MedImmune, Sanofi, Pfizer, Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Roche, AstraZeneca; Non-Financial Interests, Personal, Other, Uncompensated Relationship: Merck. J. Mazieres: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Pfizer, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen; Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Pierre Fabre, BMS, Illumina. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi Sankyo, GSK, Lilly, MSD, Merck, Mirati, Novartis, Pfizer, Roche, Regeneron, Sanofi; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi Sankyo, GSK, Lilly, MSD, Merck, Mirati, Novartis, Pfizer, Roche, Regeneron, Sanofi; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi Sankyo, GSK, Lilly, MSD, Merck, Mirati, Novartis, Pfizer, Roche, Regeneron, Sanofi; Non-Financial Interests, Personal, Officer: ESMO; Non-Financial Interests, Institutional, Research Funding: BMS, Boehringer-Ingelheim; Non-Financial Interests, Personal, Principal Investigator: Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi Sankyo, Beigene, GSK, Lilly, MSD, Merck, Mirati, Novartis, Roche. C. Chouaid: Financial Interests, Personal, Invited Speaker: AstraZeneca, BI, GSK, Roche, Lilly, Pfizer, MSD, BMS, Takeda, Sanfi, Daiichi, Gilead and Amgen ; Financial Interests, Personal, Advisory Board: AstraZeneca, BI, GSK, Roche, Lilly, Pfizer, MSD, BMS, Takeda, Sanfi, Daiichi, Gilead and Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Pfizer, BMS, Takeda; Financial Interests, Personal, Funding: AstraZeneca, Roche, Pfizer, BMS, Takeda. N. Reinmuth: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, GSK, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, GSK, Janssen, MSD, Merck, Pfizer, Symphogen and Takeda. L.S. Cove-Smith: Financial Interests, Personal, Invited Speaker: Lilly. D.L. Cortinovis: Financial Interests, Personal, Speaker’s Bureau: MSD, BMS; Financial Interests, Personal, Advisory Board: Roche, Seagen, Amgen, Sanofi Genzyme, AstraZeneca, Janssen. M.R. Migliorino: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Roche, Novartis, Takeda. A. Delmonte: Other, Personal, Advisory Board: Novartis, Takeda, Sanofi. J. García Sanchez: Financial Interests, Personal, Invited Speaker: BMS, MSD, Takeda; Financial Interests, Personal, Advisory Board: Pfzer, Sanofi; Non-Financial Interests, Personal, Officer: ESMO; Non-Financial Interests, Personal, Principal Investigator: Pfizer. L.E. Chara Velarde: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, MSD, BMS, Pfizer, Boehringer Ingelheim, Amgen. L. Paz-Ares: Financial Interests, Personal, Ownership Interest: Altum Sequencing, Stab therapeutics; Financial Interests, Personal, Member of Board of Directors: Altum sequencing, Stab therapeutics; Financial Interests, Personal, Speaker, Consultant, Advisor: Lilly, MSD, Roche, PharmaMar, Merck KGaA (Darmstadt, Germany), AstraZeneca, Novartis, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, Regeneron, Sanofi; Financial Interests, Personal, Research Grant: MSD, AstraZeneca, BMS, Pfizer, PharmaMar. P. Chander: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. I. Diaz Perez: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. K. Foroutanpour: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. C. Faivre-Finn: Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune, Elekta, MSD; Financial Interests, Institutional, Advisory Role: AstraZeneca/MedImmune, MSD. All other authors have declared no conflicts of interest.