Abstract 150P
Background
This study aimed to investigate the potential of pCR and MPR as surrogate endpoints for event-free survival (EFS) and overall survival (OS) in neoadjuvant/perioperative chemoimmunotherapy trials for NSCLC.
Methods
Systematic literature research of randomized neoadjuvant/perioperative chemoimmunotherapy trials for early-stage NSCLC was carried out in November 2024. After reconstruction of individual patient-level data from eligible trials, using a two-stage meta-analytic model, we assessed the surrogacy of pCR and MPR at both the outcome-level (i.e., the pCR and MPR are correlated with EFS and OS irrespective of treatment) and the trial-level (i.e., treatment effects on survival [Hazard Ratio] and response [Odds Ratio] endpoints are correlated).
Results
Out of 6005 records screened, a total of 8 trials were included (NADIM II, AEGEAN, NEOTORCH, KN671, CM77 T, CM816, RATIONALE315, TD-FOREKNOW), comprising 3247 patients. At the outcome-level (6 trials, n=2700), 358 (13.3%) experienced a pCR. Patients with pCR had lower risk of experiencing an EFS event compared to patients not obtaining a pCR (HR 0.17, 95% CI 0.12–0.23, p < 0.0001). At the trial-level (all 8 trials), a moderate correlation was observed between the effect of treatment on pCR and the effect of treatment on EFS (R2 0.30, 95% CI 0.00–0.63). Similar results were obtained in the OS analysis both at the outcome level (1 trial, n=86; HR 0.05, 95% CI 0.01–0.87, p=0.002) and at the trial level (6 trials, n=2838; R2 0.40, 95% CI 0.00–0.71). At the outcome-level (3 trials, n=1516), 388 (25.6%) patients experienced a MPR. Patients with MPR had lower risk of experiencing an EFS event compared to patients not obtaining a MPR (HR 0.22, 95% CI 0.17–0.29, p < 0.0001). At the trial-level (all 8 trials), a good correlation was observed between the effect of treatment on MPR and the effect of treatment on EFS (R2 0.54, 95% CI 0.00–0.76).
Conclusions
Although patients attaining a pathologic response have better outcomes, our results indicate that pCR and MPR are not sufficiently correlated with survival endpoints to justify routine use as fully validated surrogate endpoints in immunotherapy trials for early-stage NSCLC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Tagliamento: Financial Interests, Personal, Other, Consulting: Oncotech; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Takeda; Non-Financial Interests, Personal, Member, International Lung Cancer Foundation Fellow: IASLC; Non-Financial Interests, Personal, Member, Lung Cancer Group: EORTC; Non-Financial Interests, Personal, Member, Education Committee member: IASLC; Other, Personal, Other, Travel and accommodation expenses: Eli Lilly, Takeda, OSE Immunotherapeutics. M. Lambertini: Financial Interests, Personal, Advisory Board, Including both Roche Pharma and Roche Diagnostics: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Menarini, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche, AstraZeneca, Menarini, Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2023 and ASCO 2024: Daiichi Sankyo; Financial Interests, Personal, Other, Travel grant to attend SABCS 2023: Roche; Financial Interests, Institutional, Invited Speaker, 2-year research grant paid to my Institution: Gilead; Non-Financial Interests, Personal, Member of Board of Directors, Member of the national council of the Italian Association of Medical Oncology (AIOM): AIOM. R. Ferrara: Financial Interests, Personal, Advisory Board, In April 2022: MSD; Financial Interests, Personal, Advisory Board: BeiGene, BMS, Sanofi, AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD, Pfizer, AstraZeneca, Roche, Sanofi, Novartis, BMS, IPSEN, Daiichi Sankyo Company. M. Brandão: Financial Interests, Institutional, Advisory Board, 03/2023: Sanofi; Financial Interests, Institutional, Invited Speaker, 01/2023: Takeda; Financial Interests, Institutional, Invited Speaker, 05/2023: Pfizer; Financial Interests, Institutional, Invited Speaker, June 2023: BMS; Financial Interests, Institutional, Invited Speaker, September 2023: BMS; Financial Interests, Institutional, Invited Speaker, October 2023: AstraZeneca, BMS; Financial Interests, Institutional, Invited Speaker, December 2023: Janssen; Financial Interests, Institutional, Advisory Board, Oct 2023: Amgen; Financial Interests, Institutional, Advisory Board, Dec 2023: Daiichi Sankyo Financial Interests, Institutional, Invited Speaker, 01/2024 - Coimbra Thoracic IO meeting: MSD; Financial Interests, Institutional, Advisory Board, Feb and March 2024: AstraZeneca; Financial Interests, Institutional, Invited Speaker, 05/2024: MSD; Financial Interests, Institutional, Advisory Board, 05/2024: Janssen; Financial Interests, Institutional, Advisory Board, 06 and 09/2024: Inhatarget; Financial Interests, Institutional, Advisory Board, 07/2024: Pfizer; Financial Interests, Institutional, Advisory Board, 10/2024: AstraZeneca; Financial Interests, Institutional, Invited Speaker, ARTEMIDE-01 trial: AstraZeneca; Financial Interests, Institutional, Invited Speaker, IMforte trial: Roche; Financial Interests, Institutional, Invited Speaker, Beamion-Lung01 and Beamion-Lung02: Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker, CARMEN-LC: Sanofi; Financial Interests, Institutional, Invited Speaker, MCLA-129-CL01: Merus; Financial Interests, Institutional, Invited Speaker, DDriver: Merck; Financial Interests, Institutional, Invited Speaker, VERT-001: Pierre Fabre; Non-Financial Interests, Personal, Leadership Role, EORTC Lung Cancer Group - Young and Early Career group Chair (since January 2022): EORTC. I. Schmitt-Opitz: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Intuitive; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, BMS, Medtronic; Financial Interests, Personal, Other, Proctorship: Intuitive; Financial Interests, Personal, Other, International Director. Money donated back to Association: American Association for Thoracic Surgery (AATS); Financial Interests, Institutional, Research Grant: Medtronic, Roche; Non-Financial Interests, Personal, Member of Board of Directors: ESTS; Non-Financial Interests, Personal, Other, Member of Research Council: Swiss National Science Foundation; Non-Financial Interests, Personal, Other, Chair Mesothelioma group: ETOP; Non-Financial Interests, Personal, Other, Taskforce Mesothelioma, Staging Subcommittee MPM and N status for NSCLC: IASLC; Non-Financial Interests, Personal, Other, Board member: iMig; Non-Financial Interests, Personal, Other, Stiftungsrat: Schulthess Klinik; Non-Financial Interests, Personal, Other, Associate Editor: JTCVS; Non-Financial Interests, Personal, Other, Steering Committee: Roche Genentech. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Amgen, Bayer, AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Boehringer Ingelheim, Pfizer, MSD; Financial Interests, Institutional, Invited Speaker: Lilly, Eli Lilly, Lilly, Amgen, Daiichi Sankyo, Roche, Roche, JNJ, Mirati, Bayer, Eli Lilly, Amgen; Financial Interests, Institutional, Other, IDMC: Roche; Financial Interests, Institutional, Expert Testimony: Mirati; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Personal, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Personal, Member: IASLC, ASCO, AACR, ERS. B. Besse: Financial Interests, Institutional, Advisory Board: AbbVie, BioNTech SE, Beijing Aviston Biotechnology, Bristol Myer Squibb, CureVac AG, PharmaMar, Sanofi Aventis, Regeneron; Financial Interests, Institutional, Expert Testimony: AbbVie, Bristol Myer Squibb, Eli Lilly, Ellipse pharma Ltd, CureVac AG, F. Hoffmann-La Roche Ltd, Foghorn Therapeutics Inc., Genmab, Immunocore, Owkin, Sanofi; Financial Interests, Institutional, Invited Speaker: AbbVie, AstraZeneca, Bristol Myer Squibb, MSD, Daiichi Sankyo, Eli Lilly, OSE Immunotherapeutics, Sanofi, Servier, OSE Immunotherapeutics, Sanofi, Takeda, Genmab, Taiho, AstraZeneca, Amgen, BeiGene, CureVac, Janssen, MSD, PharmaMar, Eli Lilly, Daiichi Sankyo, Enliven, Nuvalent, Ellipsis, Prelude Therapeutics; Non-Financial Interests, Personal, Leadership Role, Chair of the Scientific Chairs Council: EORTC; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Board: IFCT. S. Michiels: Financial Interests, Personal, Other, DSMB member: Servier, Biophytis, Yuhan, IQVIA, Kedrion; Financial Interests, Personal, Advisory Board, Study Scientific Committee member: Roche. E. Blondeaux: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Research Grant, Research grant to my Institution for a research project: Gilead Science. All other authors have declared no conflicts of interest.