Radiotherapy (RT) patterns and factors associated with pneumonitis in PACIFIC-R, a real-world study of patients (pts) with Stage III unresectable non-small cell lung cancer (UR-NSCLC) treated with durvalumab (D) after chemoradiotherapy (CRT)

BackgroundData on RT planning has been limited in real-world settings. Pneumonitis is a complication of both RT and immunotherapy (IO), and the cause of pneumonitis after receipt of RT and IO is often ambiguous. PACIFIC-R (NCT03798535) is an ongoing, retrospective, observational study evaluating the efficacy and safety of D after CRT in pts with Stage III UR-NSCLC enrolled in an early access programme. We report exploratory analyses of RT treatment patterns and factors associated with symptomatic pneumonitis (SP) in PACIFIC-R.MethodsAs of 30 Nov 2021, 1,154 pts were enrolled. Analyses used the non-missing analysis set of 268 pts with no missing data for candidate risk factors for SP, defined as pneumonitis either of grade ≥2 or treated with corticosteroids, that developed during the D treatment period. Descriptive statistics were applied to baseline, clinical, and RT-related characteristics. Multivariable logistic regression was used to identify factors associated with SP.ResultsRates of intensity-modulated RT (IMRT) vs 3D conformal RT (3DCRT) varied by region (Table); for example, pts in France tended to receive 3DCRT while pts in the Netherlands tended to receive IMRT. Pts who received IMRT tended to be older, have more advanced disease, longer time from end of RT to the start of D, and fewer CRT interruptions than pts who received 3DCRT (Table). The risk of SP was 19.4%. Prior chronic obstructive pulmonary disease (COPD; odds ratio [OR] 2.60; 95% confidence interval [CI] 1.21, 5.65) and higher mean lung RT dose (OR 4.73; 95% CI 1.66, 15.07) were associated with higher odds of SP. Table: 1247P Characteristic 3DCRT (n=69) IMRT (n=179) Other (n=20) Age ≥65 years, n (%) 32 (46.4) 99 (55.3) 12 (60) ECOG PS ≥1, n (%) 42 (60.9) 82 (45.8) 8 (40) Median tumour size (range), mm 41 (5–130) 47 (1–129) 39.5 (10–86) T4 tumour, n (%) 17 (24.6) 74 (41.3) 5 (25) Sequential CRT, n (%) 5 (7.2) 31 (17.3) 0 Median time from RT end to D start (range), days 48 (4–118) 57 (12–241) 59.5 (30–109) Interruption of CRT, n (%) 11 (15.9) 7 (3.9) 1 (5) Country, n (%) Australia 12 (17.4) 17 (9.5) 1 (5) Belgium 7 (10.1) 17 (9.5) 1 (5) Switzerland 0 5 (2.8) 0 Germany 0 4 (2.2) 0 France 37 (53.6) 29 (16.2) 3 (15) United Kingdom 2 (2.9) 10 (5.6) 3 (15) Israel 1 (1.4) 23 (12.8) 0 Italy 2 (2.9) 14 (7.8) 0 Netherlands 4 (5.8) 56 (31.3) 0 Norway 4 (5.8) 4 (2.2) 12 (60) ConclusionsThese data suggest that RT modality varies based on patient characteristics and region. Prior COPD and higher mean lung RT dose were associated with higher odds of SP. Association between mean lung RT dose and SP indicates a need for strategic RT planning in this setting.Clinical trial identificationNCT03798535 (release date: January 10, 2019).Editorial acknowledgementMedical 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, and was funded by AstraZeneca.Legal entity responsible for the studyAstraZeneca.FundingAstraZeneca.DisclosureA.R. Filippi: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Role: Radiomics (OncoRadiomics); Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca, Roche, MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Institutional, Local PI: AstraZeneca, Roche, MSD; Non-Financial Interests, Personal, Membership or affiliation: ESMO, ESTRO, IASLC; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Takeda; Financial Interests, Personal, Steering Committee Member: AstraZeneca, EORTC. J. Bar: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Causalis, MSD, Merck Serono, Novartis, Roche, Takeda; Non-Financial Interests, Personal and Institutional, Principal Investigator: AbbVie, Amgen, AstraZeneca, Bayer, MSD, Roche, Takeda; Financial Interests, Institutional, Research Funding: Immunai, OncoHost, MSD, AstraZeneca. D.C. Christoph: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Ipsen, Merck, MSD Sharp & Dohme, Novocure, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Ipsen, Merck, MSD Sharp & Dohme, Novocure, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Takeda; Financial Interests, Personal, Expert Testimony: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Ipsen, Merck, MSD Sharp & Dohme, Novocure, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Ipsen, Merck, MSD Sharp & Dohme, Novocure, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Takeda; Non-Financial Interests, Personal, Local PI: AstraZeneca, Bristol Myers Squibb, MSD Sharp & Dohme, Novocure, Pierre Fabre, Pfizer, Roche, Sanofi; Non-Financial Interests, Personal, Membership or affiliation: IASLC, DGHO, ESMO, IASLC; Non-Financial Interests, Personal, Non-financial benefits: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck, MSD Sharp & Dohme, Pfizer, Roche, Sanofi, Takeda; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Bristol Myers Squibb, MSD Sharp & Dohme, Novocure, Pierre Fabre, Pfizer, Roche, Sanofi; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Ipsen, Merck, MSD Sharp & Dohme, Novocure, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Ipsen, Merck, MSD Sharp & Dohme, Novocure, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Takeda. R. Fietkau: Financial Interests, Personal, Advisory Board: MSD, Merck, AstraZeneca, Novocure, Sennewald; Financial Interests, Personal, Invited Speaker: Siemens Sennewald; Financial Interests, Personal and Institutional, Principal Investigator: Siemens; MSD; Merck; Novocure ; AstraZeneca; Financial Interests, Personal and Institutional, Research Funding: Siemens; MSD; Merck; Novocure; AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Siemens; MSD; Merck; Novocure; AstraZeneca; Financial Interests, Personal and Institutional, Speaker’s Bureau: Siemens; MSD; Merck; Novocure; AstraZeneca. M.C. Garassino: Financial Interests, Personal, Other: AstraZeneca, Abion, MSD International GmbH, Bayer, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Incyte, Novartis, Pfizer, Roche, Takeda, Seattle Genetics, Mirati, Daiichi Sankyo, Regeneron, Merck, Blueprint, Janssen, Sanofi, AbbVie, BeiGeni; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Abion, MSD International GmbH, Bayer, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Incyte, Novartis, Pfizer, Roche, Takeda, Seattle Genetics, Mirati, Daiichi Sankyo, Regeneron, Merck, Blueprint, Janssen, Sanofi, AbbVie, BeiGeni; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Abion, MSD International GmbH, Bayer, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Incyte, Novartis, Pfizer, Roche, Takeda, Seattle Genetics, Mirati, Daiichi Sankyo, Regeneron, Merck, Blueprint, Janssen, Sanofi, AbbVie, BeiGeni. P. Garrido Lopez: Financial Interests, Personal, Speaker’s Bureau: Janssen, MSD, Novartis, Medscape, Takeda, TouchTime, Medscape; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, Roche, Janssen; Financial Interests, Personal, Advisory Role: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and Takeda; Financial Interests, Personal, Steering Committee Member: Novartis, IO Biotech IO102-Janssen. V.D. Haakensen: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Novartis; Financial Interests, Personal, Local PI: AstraZeneca, Lilly, MSD, Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Pfizer, BMS, MSD, Janssen. S.C. Kao: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, MSD, BMS, Roche, Amgen, Beigene, Boehringer Ingelheim, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: MSD, BMS, Roche, AstraZeneca, Pfizer, Takeda, Beigene, Daiichi Sankyo; Financial Interests, Personal, Principal Investigator: AstraZeneca, MSD, BMS, Daiichi Sankyo, Roche, Beigene; Financial Interests, Institutional, Research Grant: AstraZeneca. F. McDonald: Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca. M. Moskovitz: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Takeda, Bayer, Amgen, Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Non-Financial Interests, Personal, Local PI: MSD; Financial Interests, Personal, Other, Honorarium: BMS, MSD, Roche, AstraZeneca, Merck, AbbVie, Takeda, Janssen; Financial Interests, Personal, Research Grant: BMS. S. Peters: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Arcus, AstraZeneca, Bayer, Beigene, BerGenBio, Biocartis, BioInvent, Biontech, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Debiopharm, Eli Lilly, F-Star, Foundation Medicine, Genzyme, Gilead, GSK, Hutchmed, Illumina, Incyte, Ipsen, iTeos, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Novocure, Nykode Therapeutics, PharmaMar, Promontory Therapeutics, Pfizer, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, Takeda; Other, Institutional, Coordinating PI: Amgen, Arcus, AstraZeneca, Beigene, Bristol Myers Squibb, GSK, iTeos, Merck Sharp and Dohme, Mirati, PharmaMar, Promontory Therapeutics, Roche/Genentech, Seattle Genetics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Foundation Medicine, GSK, Illumina, Ipsen, Merck Sharp and Dohme, Mirati, Novartis, Pfizer, Roche/Genentech, Sanofi, Takeda; Financial Interests, Institutional, Steering Committee Member: Arcus, AstraZeneca, Beigene, Biontech, Bristol Myers Squibb, Eli Lilly, F-Star, Gilead, GSK, iTeos, Merck Sharp and Dohme, Mirati, PharmaMar, Pfizer, Regeneron, Roche/Genentech, Seattle Genetics, Takeda. P. Vercauter: Financial Interests, Institutional, Principal Investigator: AstraZeneca, Daiichi Sankyo, Roche; Financial Interests, Institutional, Research Grant: Chiesi; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb. H.J.M. Smit: Financial Interests, Personal, Advisory Board: MSD, BMS, AstraZeneca, Amgen; Financial Interests, Institutional, Coordinating PI: MSD; Financial Interests, Institutional, Research Funding: MSD. P. Chander: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Institutional, Stocks/Shares: AstraZeneca. Y. Qiao: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Institutional, Stocks/Shares: AstraZeneca. J. Faria: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. N. Girard: Financial Interests, Personal, Full or part-time Employment, Immediate family member: AstraZeneca; Financial Interests, Personal, Other, Consultation fees: AbbVie, Amgen, AstraZeneca, Beigene, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Ipsen Hoffmann-La Roche, Janssen, LeoPharma, Lilly, Merck Sharp & Dohme, Mirati, Novartis, Pfizer, Pierre Fabre, Sanofi, Takeda; Financial Interests, Institutional, Research Grant: AbbVie, Amgen, AstraZeneca, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Hoffmann-La Roche, Janssen, LeoPharma, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Sanofi, Sivan. All other authors have declared no conflicts of interest.