108MO - Safety and efficacy outcomes with durvalumab after sequential chemoradiotherapy (sCRT) in stage III, unresectable NSCLC (PACIFIC-6)

Background

In the ph 3, placebo-controlled PACIFIC trial, durvalumab (durva) after concurrent CRT (cCRT) significantly improved survival in pts with Stage III, unresectable NSCLC, with manageable safety. As many pts are ineligible for cCRT, the ph 2 PACIFIC-6 trial (NCT03693300) aims to assess safety with durva after sCRT. We report the primary safety analysis and secondary efficacy analyses from PACIFIC-6.

Methods

Pts with ECOG PS ≤2 and no progression after platinum-based sCRT were enrolled to receive durva 1500mg IV q4w ≤24 months or until progression, unacceptable toxicity or consent withdrawal. The primary endpoint was safety/tolerability of durva, defined by the incidence of grade 3/4 possibly related AEs (PRAEs) occurring within 6 months of treatment (Tx) initiation. PFS and ORR (investigator assessed; RECIST v1.1), and OS, were secondary endpoints. PFS and OS were analysed by Kaplan–Meier method.

Results

As of July 15, 2021, 117 pts were enrolled; 114 (97.4%) had PS 0/1 and 3 (2.6%) had PS 2. Median age was 68.0 years (65.8% were aged ≥65), 62.4% were male and 37.6%/50.4%/11.1% had Stage IIIA/B/C NSCLC. 98.3% had past/present medical conditions, mostly vascular (59.0%), respiratory (53.8%) and metabolic (51.3%) disorders. Median Tx duration was 32.0 weeks (37.6% were ongoing Tx at data cutoff). In all, 94.9% of pts had any AEs and 76.9% had PRAEs. 18.8% had grade 3/4 AEs and 4.3% had grade 3/4 PRAEs (1.7% had grade 3/4 PRAE pneumonitis); all pts with grade 3/4 PRAEs had these events occur within 6 months (4.3%; 95% CI, 1.4–9.7). 21.4% and 16.2% had AEs and PRAEs leading to Tx discontinuation, respectively; pneumonitis was the most common PRAE leading to discontinuation (10.3%). 2 pts (1.7%) had fatal AEs; 1 was a PRAE (pneumonitis). Efficacy outcomes are listed in the table. Table: 108MO

*Median follow-up among pts censored for PFS = 11.0 months (range, <0.1–22.3 months).^†Median follow-up among pts censored for OS = 13.3 months (range, 4.4–25.6 months). ^‡47/114 (41.2%) had PS 0 and 67/114 (58.8%) had PS 1. ^§95% CI for ORR was calculated using the Clopper–Pearson method. CI, confidence interval; NC, not calculable.

Conclusions

Durva after sCRT had a similar safety profile to that observed with durva after cCRT in the PACIFIC trial and showed encouraging preliminary efficacy in a frailer and older population.

Clinical trial identification

NCT03693300.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Nina Kratky and Aaron Korpal of Ashfield MedComms (Manchester, UK), an Ashfield Health Company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M.C. Garassino: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: MSD International GmbH; Financial Interests, Personal, Other: Bristol Myers Squibb; Financial Interests, Personal, Other: Boehringer Ingelheim Italia S.p.A; Financial Interests, Personal, Other: Celgene; Financial Interests, Personal, Other: Eli Lilly; Financial Interests, Personal, Other: Ignyta; Financial Interests, Personal, Other: Incyte; Financial Interests, Personal, Other: Inivata; Financial Interests, Personal, Other: MedImmune; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Takeda; Financial Interests, Personal, Other: Seattle Genetics; Financial Interests, Personal, Other: Mirati; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Regerenon; Financial Interests, Personal, Other: Merck; Financial Interests, Institutional, Other: Eli Lilly; Financial Interests, Institutional, Other: MSD; Financial Interests, Institutional, Other: Pfizer (MISP); Financial Interests, Institutional, Other: AstraZeneca; Financial Interests, Institutional, Other: MSD International GmbH; Financial Interests, Institutional, Other: Bristol Myers Squibb; Financial Interests, Institutional, Other: Boehringer Ingelheim Italia S.p.A; Financial Interests, Institutional, Other: Celgene; Financial Interests, Institutional, Other: Eli Lilly; Financial Interests, Institutional, Other: Ignyta; Financial Interests, Institutional, Other: Incyte; Financial Interests, Institutional, Other: MedImmune; Financial Interests, Institutional, Other: Novartis; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Takeda; Financial Interests, Institutional, Other: Tiziana; Financial Interests, Institutional, Other: Foundation Medicine; Financial Interests, Institutional, Other: Glaxo Smith Kline; Financial Interests, Institutional, Other: Spectrum Pharmaceuticals; Other, Institutional, Research Grant: AIRC; Other, Institutional, Research Grant: AIFA; Other, Institutional, Research Grant: Italian Moh; Other, Institutional, Research Grant: TRANSCAN. J. Mazieres: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Daiichi; Non-Financial Interests, Personal, Research Grant: AstraZeneca; Non-Financial Interests, Personal, Research Grant: Pierre Fabre; Non-Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Principal Investigator: Takeda; Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Principal Investigator: Lilly; Financial Interests, Personal, Principal Investigator: Daiichi; Financial Interests, Personal, Principal Investigator: Boehringer Ingelheim; Financial Interests, Personal, Principal Investigator: Sanofi; Financial Interests, Personal, Principal Investigator: Hengrui Therapeutics; Financial Interests, Personal, Principal Investigator: Spectrum. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Beigene; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Mirati; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Beigene; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Mirati; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Non-Financial Interests, Institutional, Principal Investigator: Amgen; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Institutional, Principal Investigator: Beigene; Non-Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim; Non-Financial Interests, Institutional, Principal Investigator: Lilly; Non-Financial Interests, Institutional, Principal Investigator: Merck; Non-Financial Interests, Institutional, Principal Investigator: MSD; Non-Financial Interests, Institutional, Principal Investigator: Mirati; Non-Financial Interests, Institutional, Principal Investigator: Novartis; Non-Financial Interests, Institutional, Principal Investigator: Pfizer; Non-Financial Interests, Institutional, Principal Investigator: Sanofi; Non-Financial Interests, Institutional, Principal Investigator: Roche; Non-Financial Interests, Institutional, Principal Investigator: Daiichi; Non-Financial Interests, Institutional, Principal Investigator: Nektar. C. Chouaid: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Sanofi Aventis; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi-Aventis; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: GSK; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Sanofi-Aventis; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Lilly; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Takeda; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Sponsor/Funding: AstraZeneca; Financial Interests, Personal, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Personal, Sponsor/Funding: GSK; Financial Interests, Personal, Sponsor/Funding: Roche; Financial Interests, Personal, Sponsor/Funding: Sanofi-Aventis; Financial Interests, Personal, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Personal, Sponsor/Funding: MSD; Financial Interests, Personal, Sponsor/Funding: Lilly; Financial Interests, Personal, Sponsor/Funding: Novartis; Financial Interests, Personal, Sponsor/Funding: Pfizer; Financial Interests, Personal, Sponsor/Funding: Takeda; Financial Interests, Personal, Sponsor/Funding: Bayer; Financial Interests, Personal, Sponsor/Funding: Janssen; Financial Interests, Personal, Sponsor/Funding: Amgen. N. Reinmuth: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Hoffman-La Roche; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Hoffman-La Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Takeda. D. Cortinovis: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche. M.R. Migliorino: Other, Personal, Invited Speaker: Roche; Other, Personal, Invited Speaker: Pfizer; Other, Personal, Invited Speaker: AstraZeneca; Other, Personal, Invited Speaker: Takeda; Other, Personal, Advisory Board: Pfizer; Other, Personal, Advisory Board: Takeda; Other, Personal, Advisory Board: Roche. J. Garcia Sánchez: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: EUSA Pharma; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Eisai Europe. L.E. Chara Velarde: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: Roche. R. Bernabe: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb. L. Paz-Ares: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Mirati; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: PharmaMar; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Member of the Board of Directors: Genomica; Financial Interests, Personal, Member of the Board of Directors: Altum Sequency; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. I. Diaz Perez: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N. Trunova: 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, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Elekta. All other authors have declared no conflicts of interest.