1359P - Lack of Abscopal effect and radiotherapy-induced lymphocyte depletion in advanced non-small cell lung cancer (NSCLC) patients treated with atezolizumab and radiotherapy

Background

The abscopal effect, a systemic immune response in metastatic cancer induced by local irradiation, suggested since 1953 was mainly supported by individual case reports. With a lack of definitive evidence for this phenomenon, we set out to identify a potential mechanism by investigating the immune cell dynamics in the context of prior and on-study radiotherapy (RT) in metastatic NSCLC patients treated with atezolizumab.

Methods

In this post-hoc analysis more than 3’000 NSCLC patients were included from three phase III trials (IMpower130, IMpower150, OAK) with squamous and non-squamous cell histology. These studies investigated the efficacy of the anti-PD-L1 inhibitor atezolizumab in combination with various first-line chemotherapies or as second-line monotherapy. The current work analyzed the influence of prior RT on efficacy and baseline values of the absolute lymphocyte count (ALC), absolute neutrophil count (ANC), neutrophil-to-lymphocyte ratio (NLR) as well as their dynamics during on-study RT.

Results

Prior RT was associated with significantly reduced baseline ALC values irrespective of the treatment and time of application without observing any improvements of key outcome parameters such as overall survival, progression-free survival or overall response rate (Table). This lymphocyte depleting effect of RT ultimately translated into increased NLRs, an established prognostic factor for NSCLC patients under ICI treatment with higher values being associated with unfavorable treatment results. Similar effects on ALC and NLR with a comparable magnitude were observed for on-study RT. Table: 1359P

ALC & NLR in G/LA Atezolizumab, B Bevacizumab, C Carboplatin, P Paclitaxel, NP Nab-P, D Docetaxel# HR and p-values are stratified

Conclusions

Whether applied during or before the initiation of ICI treatment RT significantly reduced the number of lymphocytes. The depletion of immune checkpoint inhibitor effector cells might explain the absence of any measurable abscopal effect with RT, the way how it is currently utilized.

Clinical trial identification

NCT02367781 (IMpower130), NCT02366143 (IMpower150), NCT02008227 (OAK).

Editorial acknowledgement

Legal entity responsible for the study

Alexander Meisel.

Funding

Kantonsspital Graubünden + Gerresheimer.

Disclosure

A. Meisel: Financial Interests, Personal, Advisory Board, Advisory, Consulting or Speaker: for Amgen, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Gerresheimer, GSK, Janssen, Merck, MSD, Novartis, Roche, Regeneron, Sanofi, Servier, Takeda and Vifor; Financial Interests, Personal, Research Funding: Bayer; Financial Interests, Institutional, Research Funding: Merck & Cie; Financial Interests, Personal, Other, Intellectual Property interest: Merck & Cie; Financial Interests, Personal, Other, Provided expert testimony: Sanofi; Financial Interests, Personal, Other, travel/accommodation expenses: Amgen, Astellas, Boehringer Ingelheim, Janssen, Merck, Roche, Sanofi and Servier. R. von Moos: Financial Interests, Personal, Advisory Board: Amgen, Roche, Gilead, Pierre Fabre Pharma Mar, Sanofi, MSD, Eli Lilly, Merck, Vifor, GSK; Financial Interests, Personal, Research Grant: Bayer and Merck Serono; Financial Interests, Personal, Advisory Board, Travel support: Pierre Fabre, Takeda. A. Haider: Financial Interests, Personal, Other, Employer: Roche Pharma AG. R. Abedian: Financial Interests, Institutional, Other, Employer: Sensile Medical AG; Financial Interests, Institutional, Other, Employer: Gerresheimer. S. Websky: Financial Interests, Personal, Other, Employer: Gerresheimer. S.I. Rothschild: Financial Interests, Institutional, Other, Honoraria: Roche Pharma AG, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, MSD Oncology, Novartis, Amgen, Lilly, Eisai, Merck Serono, Pfizer, Takeda, Bayer, Janssen Oncology, Otsuka, PharmaMar, Sanofi; Financial Interests, Institutional, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Eisai, Eli Lilly, Merck Serono, MSD Oncology, Novartis, Roche Pharma AG, Takeda, Amgen, Otsuka, PharmaMar; Financial Interests, Institutional, Speaker’s Bureau: Roche Pharma AG, Sanofi/Aventis, Amgen, AstraZeneca, Takeda; Financial Interests, Research Funding: AbbVie, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Merck Serono, Roche Pharma AG; Financial Interests, Other, Travel, Accommodation, Expenses: Sanofi, Roche Pharma AG, Bristol Myers Squibb, MSD Oncology, AstraZeneca, Takeda, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Other: Federal Drug Comission of the Federal Office of Public Health; Financial Interests, Institutional, Other: Swiss Group for Clinical Cancer Research (SAKK). M.J. Hochmair: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, Lilly, Amgen, Takeda; Financial Interests, Personal, Other: Consultant: Roche, BMS, MSD, Lilly, Amgen, Takeda; Financial Interests, Personal, Speaker’s Bureau: Roche, BMS, MSD, Lilly, Amgen, Takeda. D.R. Gandara: Financial Interests, Institutional, Research Grant: Amgen AstraZeneca Genentech Merck; Financial Interests, Institutional, Advisory Board: Adagene, Inc. (institutional) AstraZeneca (institutional) Roche-Genentech (institutional) Guardant Health (institutional) IO Biotech (institutional) Oncocyte (institutional) OncoHost (institutional); Financial Interests, Personal, Advisory Board, Consultant: Merck (consultant). F. Cappuzzo: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, Galecto and MSD,; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi, GSK, Pfizer; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, BioNTech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Roche, Sanofi, GSK, Lilly; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Amgen, Boehringer-Ingelheim, BeiGene, Daiichi Sankyo, GSK, BMS, Lilly, MSD, Regeneron, Roche; Financial Interests, Institutional, Local PI: Pfizer Seagen. F. Stenner-Liewen: Financial Interests, Personal, Advisory Board: Bayer, BMS, Janssen, MSD, AstraZeneca and Sanofi; Financial Interests, Personal, Other, travel/other expenses: BMS, Sanofi, and Roche. M.T. Mark: Financial Interests, Personal, Advisory Role: Janssen, Roche, Takeda, BMS, MSD, AstraZeneca, Merck; Financial Interests, Institutional, Research Grant: Gilead Science; Financial Interests, Personal, Other, Travel Grant: Janssen, AstraZeneca, Roche, Takeda, Amgen. All other authors have declared no conflicts of interest.