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Poster Display session

32P - Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC: A systematic review and meta-analysis

Date

03 Apr 2022

Session

Poster Display session

Presenters

Urania Dafni

Citation

Annals of Oncology (2022) 33 (suppl_2): S27-S70. 10.1016/annonc/annonc856

Authors

U. Dafni1, R.A. Soo2, S. Peters3, Z. Tsourti4, K. Vervita4, J. Han5, J. De Castro6, L. Coate7, M. Früh8, S.M.S. Hashemi9, E. Nadal10, E. Carcereny11, M. Angeles Sala González12, R. Bernabe Caro13, M. Provencio Pulla14, S. Cuffe15, B. Ruepp16, H. Roschitzki-Voser16, R. Rosell17, R.A. Stahel18

Author affiliations

  • 1 National and Kapodistrian University & Frontier Science Foundation Hellas, Athens/GR
  • 2 National University Cancer Institute, Singapore/SG
  • 3 CHUV - Centre Hospitalier Universitaire Vaudois, Lausanne/CH
  • 4 Frontier Science Foundation Hellas, Athens/GR
  • 5 The Center for Lung Cancer, National Cancer Center, Goyang/KR
  • 6 Hospital Universitario La Paz, Madrid/ES
  • 7 University Hospital Limerick, Limerick/IE
  • 8 Cantonal Hospital St. Gallen, St.Gallen/CH
  • 9 Amsterdam UMC, VU University Medical Center, Amsterdam/NL
  • 10 ICO L'Hospitalet, 08908 - Barcelona/ES
  • 11 ICO - Institut Català d'Oncologia Badalona, Badalona/ES
  • 12 Hospital Universitario Basurto, Bilbao/ES
  • 13 Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 14 University Hospital Puerta de Hierro Majadahonda, Majadahonda/ES
  • 15 St. James's Hospital, Dublin/IE
  • 16 European Thoracic Oncology Platform (ETOP), Bern/CH
  • 17 Catalan Institute of Oncology (ICO), 8916 - Barcelona/ES
  • 18 Bern/CH
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Abstract 32P

Background

In the randomised BOOSTER trial, primary analysis failed to show superiority of the osimertinib(osi)/bevacizumab(beva) combination versus osi alone. Exploratory analysis found an improvement in progression-free survival (PFS) in current/ever-smokers. The role of smoking status on the benefit of adding an angiogenesis inhibitor to EGFR TKI therapy for EGFR-mutated non-small cell lung cancer (EGFR-NSCLC) patients (pts) remains undetermined.

Methods

A systematic review and meta-analysis was conducted to evaluate the relative effect of adding an angiogenesis inhibitor to EGFR TKI therapy in advanced EGFR-NSCLC pts, according to their smoking status. All relevant randomised studies of osi/erlotinib(erlo) with or without beva/ramucirumab(ramu), appearing in main oncology congresses or in PubMed as of 1st November 2021, were examined. The hazard ratios (HRs) for the primary endpoint of PFS by smoking status, were used in the analysis. Pooled HRs and the interaction HR, are estimated by fixed or random effect models, depending on the detected degree of heterogeneity.

Results

Seven randomised trials (1,291 pts) were included in the meta-analysis. Five of the studies included pts in 1st-line (erlo/beva:3; erlo/ramu and osi/beva: 1 each), and two in 2nd-line (osi/beva). All studies had EGFR-TKI alone as the control arm. For smokers (current or former, n=502), the pooled PFS HR estimate in favour of the combination was statistically significant (HR=0.55; 95% CI: 0.44-0.69; p<0.010) while for non-smokers (n=789), it was not (HR=0.92; 95% CI: 0.66-1.27; p=0.60). Importantly, a significant interaction effect of treatment by smoking was found (HRinteraction =0.62; 95% CI: 0.41-0.93, p=0.020).

Conclusions

In advanced EGFR-NSCLC smoker pts, the addition of an angiogenesis inhibitor (beva, ramu) to EGFR TKI therapy (erlo, osi) was found to provide a statistically significant PFS benefit. Whether this might be due to a specific co-mutational pattern produced by tobacco exposure remains to be determined. The biological basis for this observation should be pursued.

Clinical trial identification

NCT03133546; EudraCT 2016-002029-12.

Legal entity responsible for the study

European Thoracic Oncology Platform (ETOP) c/o IBCSG Effingerstrasse 40 3008 Bern Switzerland.

Funding

AstraZeneca (Study support + Osimertinib) and F. Hoffmann-La Roche (Bevacizumab).

Disclosure

U. Dafni: Financial Interests, Personal, Member, received honorarium: Tumor Agnostic Evidence Generation working Group of Roche. R.A. Soo: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Lily; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Taiho; Financial Interests, Personal, Advisory Role: Takedo; Financial Interests, Personal, Advisory Role: Yuhan; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Boehringer Ingelheim. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Fishawack, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, OncologyEducation, PharmaMar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Talk in a company's organized public event: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Illumina, Imedex, Medscape, Merck Sharp & Dohme, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda, Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb; Clovis, GSK, Illumina, Lilly, Merck Sharp & Dohme, Merck Serono, Mirati, Novartis, Pfizer, Phosplatin Therapeutics, Roche/Genentech. J. Han: Financial Interests, Personal, Research Grant: Hoffmann-La Roche Ltd; Financial Interests, Personal, Research Grant: Ono; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Other, Compensated as an advisor: Medpacto; Financial Interests, Personal, Other, Compensated as an advisor: Abion; Financial Interests, Personal, Other, Compensated as an advisor: Ono; Financial Interests, Personal, Other, Payment or honoraria for lectures,presentations, speakers bureaus, manuscript writing or edu. events: AstraZeneca; Financial Interests, Personal, Other, Payment or honoraria for lectures,presentations, speakers bureaus, manuscript writing or edu. events: Bristol Myers Squibb; Financial Interests, Personal, Other, Payment or honoraria for lectures,presentations, speakers bureaus, manuscript writing or edu. events: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Payment or honoraria for lectures,presentations, speakers bureaus, manuscript writing or edu. events: Merck Sharpe & Dohme; Financial Interests, Personal, Other, Payment or honoraria for lectures,presentations, speakers bureaus, manuscript writing or edu. events: Takeda; Financial Interests, Personal, Other, Payment or honoraria for lectures,presentations, speakers bureaus, manuscript writing or edu. events: Novartis. J. De Castro: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Other, personal fees: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Other, personal fees: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Merck Sharp and Dohme; Financial Interests, Personal, Other, personal fees: Merck Sharp and Dohme; Financial Interests, Personal, Research Grant: Hoffmann-La Roche; Financial Interests, Personal, Other, personal fees: Hoffmann-La Roche; Financial Interests, Personal, Other, personal fees: Bayer; Financial Interests, Personal, Other, personal fees: Boehringer Ingelheim; Financial Interests, Personal, Other, personal fees: GlaxoSmithKlein; Financial Interests, Personal, Other, personal fees: Jansen-Cilag; Financial Interests, Personal, Other, personal fees: Lilly; Financial Interests, Personal, Other, personal fees: Novartis; Financial Interests, Personal, Other, personal fees: Pfizer; Financial Interests, Personal, Other, personal fees: Takdeda. L. Coate: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Daichi. M. Früh: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Other, other support: AstraZeneca; Financial Interests, Personal, Other, other support: Bristol Myers Squibb; Financial Interests, Personal, Other, other support: Boehringer Ingelheim; Financial Interests, Personal, Other, other support: Janssen; Financial Interests, Personal, Other, other support: MSD; Financial Interests, Personal, Other, other support: Pfizer; Financial Interests, Personal, Other, other support: Roche; Financial Interests, Personal, Other, other support: Takeda. E. Nadal: Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Other, Personal fees: Roche; Non-Financial Interests, Personal, Other, non-financial support: Roche; Financial Interests, Personal, Other, personal fees: AstraZeneca; Non-Financial Interests, Personal, Other, non-financial support: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Other, personal fees: Bristol Myers Squibb; Non-Financial Interests, Personal, Other, non-financial support: Bristol Myers Squibb; Financial Interests, Personal, Other, personal fees: Merck Sharp Dohme; Non-Financial Interests, Personal, Other, non-financial support: Merck Sharp Dohme; Financial Interests, Personal, Research Grant: Merck Serono; Financial Interests, Personal, Other, personal fees: Merck Serono; Financial Interests, Personal, Other, personal fees: Takeda; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Other, personal fees: Pfizer; Non-Financial Interests, Personal, Other, non-financial support: Pfizer; Financial Interests, Personal, Other, personal fees: Lilly; Financial Interests, Personal, Other, personal fees: Bayer; Financial Interests, Personal, Other, personal fees: Amgen; Financial Interests, Personal, Other, personal fees: Boehringer Ingelheim. E. Carcereny: Financial Interests, Personal, Other, personal fees: AstraZeneca; Financial Interests, Personal, Other, personal fees: Amgen; Financial Interests, Personal, Other, personal fees: Bristol Myers Squibb; Financial Interests, Personal, Other, personal fees: MSD; Financial Interests, Personal, Other, personal fees: Roche. M. Angeles Sala González: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Other, speaker role: Pierre Fabre; Financial Interests, Personal, Other, travel grant: Roche; Financial Interests, Personal, Other, travel grant: PharmaMar. R. Bernabé Caro: Financial Interests, Personal, Other, payment or honoraria for lectures, presentations, speakers’bureaus, manuscript writing or edu. events: Roche; Financial Interests, Personal, Other, payment or honoraria for lectures, presentations, speakers’bureaus, manuscript writing or edu. events: AstraZeneca; Financial Interests, Personal, Other, payment or honoraria for lectures, presentations, speakers’bureaus, manuscript writing or edu. events: Bristol Myers Squibb; Financial Interests, Personal, Other, payment or honoraria for lectures, presentations, speakers’bureaus, manuscript writing or edu. events: Amgen; Financial Interests, Personal, Other, payment or honoraria for lectures, presentations, speakers’bureaus, manuscript writing or edu. events: MSD; Financial Interests, Personal, Other, participation on Data Safety Monitoring Board or Advisory Board: AstraZeneca; Financial Interests, Personal, Other, participation on Data Safety Monitoring Board or Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Other, participation on Data Safety Monitoring Board or Advisory Board: Roche. M. Provencio Pulla: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Other, personal fees: AstraZeneca; Financial Interests, Personal, Other, personal fees: Bristol Myers Squibb; Financial Interests, Personal, Other, personal fees: Roche; Non-Financial Interests, Personal, Other, non-financial support: AstraZeneca; Non-Financial Interests, Personal, Other, non-financial support: Bristol Myers Squibb; Non-Financial Interests, Personal, Other, non-financial support: Roche; Financial Interests, Personal, Other, personal fees: MSD; Financial Interests, Personal, Other, personal fees: Takeda. S. Cuffe: Non-Financial Interests, Personal, Other, non-financial support: Pfizer; Non-Financial Interests, Personal, Other, non-financial support: Roche; Non-Financial Interests, Personal, Other, non-financial support: MSD; Non-Financial Interests, Personal, Other, non-financial support: Bristol Myers Squibb. R.A. Stahel: Financial Interests, Personal, Advisory Role, consultant or advisory role: AstraZeneca; Financial Interests, Personal, Advisory Role, consultant or advisory role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, consultant or advisory role: Janssen; Financial Interests, Personal, Advisory Role, consultant or advisory role: MSD; Financial Interests, Personal, Advisory Role, consultant or advisory role: Pfizer; Financial Interests, Personal, Advisory Role, consultant or advisory role: Regeneron; Financial Interests, Personal, Advisory Role, consultant or advisory role: Roche; Financial Interests, Personal, Advisory Role, consultant or advisory role: Seattle Genetics; Financial Interests, Personal, Advisory Role, consultant or advisory role: Takdeda; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Blueprint; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Sandoz; Financial Interests, Personal, Other, DMC role: Genentech/Roche; Financial Interests, Personal, Other, DMC role: Takeda; Financial Interests, Personal, Other, financial support for ETOP and IBCSG trials, where he is president and scientific chair: AstraZeneca; Financial Interests, Personal, Other, financial support for ETOP and IBCSG trials, where he is president and scientific chair: Bristol Myers Squibb; Financial Interests, Personal, Other, financial support for ETOP and IBCSG trials, where he is president and scientific chair: Ipsen; Financial Interests, Personal, Other, financial support for ETOP and IBCSG trials, where he is president and scientific chair: MSD; Financial Interests, Personal, Other, financial support for ETOP and IBCSG trials, where he is president and scientific chair: Novartis; Financial Interests, Personal, Other, financial support for ETOP and IBCSG trials, where he is president and scientific chair: Pierre Fabre; Financial Interests, Personal, Other, financial support for ETOP and IBCSG trials, where he is president and scientific chair: Roche; Financial Interests, Personal, Other, financial support for ETOP and IBCSG trials, where he is president and scientific chair: Pfizer. All other authors have declared no conflicts of interest.

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