학술논문
Correlation between biomarkers and treatment outcomes in diverse cancers: a systematic review and meta-analysis of phase I and II immunotherapy clinical trials.
Document Type
Academic Journal
Author
Fountzilas E; Department of Medical Oncology, St Luke's Clinic, Thessaloniki, Greece; European University Cyprus, Limassol, Cyprus.; Vo HH; The University of Texas MD Anderson Cancer Center, Department of Investigational Cancer Therapeutics, Houston, TX, USA.; Mueller P; Department of Statistics and Data Science, The University of Texas at Austin, Austin, TX, USA.; Kurzrock R; WIN Consortium for Precision Medicine, Paris, France; Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: rkurzrock@mcw.edu.; Tsimberidou AM; The University of Texas MD Anderson Cancer Center, Department of Investigational Cancer Therapeutics, Houston, TX, USA. Electronic address: atsimber@mdanderson.org.
Source
Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0852 (Electronic) Linking ISSN: 09598049 NLM ISO Abbreviation: Eur J Cancer Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Many immuno-oncology (IO) trials are conducted without biomarker selection. We performed a meta-analysis of phase I/II clinical trials evaluating immune checkpoint inhibitors (ICIs) to determine the association between biomarkers and clinical outcomes, if any.
Methods: A PubMed search for phase I/II clinical trials with drugs approved by the Food and Drug Administration (labelled, off-label, combined with investigational ICIs or other treatment modalities) from 2018 to 2020 was performed. The objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between biomarker-positive and biomarker-negative groups, using studies that explored the correlation of biomarkers with outcomes.
Results: Overall, 174 clinical studies that included 19,178 patients were identified, and 132 studies investigated>30 correlative biomarkers that included PD-L1 expression (≥1%, 111 studies), tumour mutational burden (20 studies) and microsatellite instability/mismatch repair deficiency (10 studies). Overall, 123, 46 and 30 cohorts (drugs, tumour types or biomarkers) with 11,692, 3065, and 2256 patient outcomes for ORR, PFS and OS, respectively, were analysed in correlation with biomarkers. Meta-analyses demonstrated that ICIs in patients with biomarker-positive tumours were associated with higher ORR (odds ratio 2.15 [95% CI, 1.79-2.58], p < 0.0001); and longer PFS (hazard ratio [HR] 0.55 [95% CI, 0.45-0.67], p < 0.0001), and OS (HR 0.65 [95% CI, 0.53-0.80], p < 0.0001) compared with those with biomarker-negative tumours. Significance for ORR and PFS was retained in multivariate analysis (p < 0.001) (OS, not included owing to the small number of trials reporting OS).
Conclusion: Our data suggest that IO biomarkers should be used in patient selection for ICIs. Prospective studies are warranted.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Elena Fountzilas: Advisory Role: LEO Pharma, Amgen, DEMO. Speaker fees: Roche, Pfizer, AstraZeneca, GSK, Amgen. Stock ownership: GENPREX INC, Deciphera Pharmaceuticals, Inc. Travel grant: Genesis, Pfizer, DEMO and Astra Zeneca. Dr. Henry Hiep Vo reports no relevant conflicts of interest. Dr. Peter Mueller reports no relevant conflicts of interest. Dr. Razelle Kurzrock has the following financial relationships to disclose: Research Funding (Institution): Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Konica Minolta, Grifols, Biologic Dynamics, Boehringer Ingelheim, Medimmune, and Guardant. Consulting role: X-Biotech, Loxo, Biologic Dynamics, Turning Point, TD2, Bicara, and Actuate Therapeutics. Speaker fees: Roche. Ownership interest: IDbyDNA and CureMatch, Inc. Board member: CureMatch and CureMetrix. Dr. Apostolia-Maria Tsimberidou has the following financial relationships to disclose: Research Funding (Institution): OBI Pharma, Parker Institute for Cancer Immunotherapy, Immatics, Tvardi Therapeutics, Tempus, Boston Biomedical, Placon Therapeutics, Karus Therapeutics and Agenus. Consulting or Advisory Role: Vincerx, Diaccurate, BrYet, Avstera, Macrogenics, Bioeclipse, Nex-I.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Methods: A PubMed search for phase I/II clinical trials with drugs approved by the Food and Drug Administration (labelled, off-label, combined with investigational ICIs or other treatment modalities) from 2018 to 2020 was performed. The objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between biomarker-positive and biomarker-negative groups, using studies that explored the correlation of biomarkers with outcomes.
Results: Overall, 174 clinical studies that included 19,178 patients were identified, and 132 studies investigated>30 correlative biomarkers that included PD-L1 expression (≥1%, 111 studies), tumour mutational burden (20 studies) and microsatellite instability/mismatch repair deficiency (10 studies). Overall, 123, 46 and 30 cohorts (drugs, tumour types or biomarkers) with 11,692, 3065, and 2256 patient outcomes for ORR, PFS and OS, respectively, were analysed in correlation with biomarkers. Meta-analyses demonstrated that ICIs in patients with biomarker-positive tumours were associated with higher ORR (odds ratio 2.15 [95% CI, 1.79-2.58], p < 0.0001); and longer PFS (hazard ratio [HR] 0.55 [95% CI, 0.45-0.67], p < 0.0001), and OS (HR 0.65 [95% CI, 0.53-0.80], p < 0.0001) compared with those with biomarker-negative tumours. Significance for ORR and PFS was retained in multivariate analysis (p < 0.001) (OS, not included owing to the small number of trials reporting OS).
Conclusion: Our data suggest that IO biomarkers should be used in patient selection for ICIs. Prospective studies are warranted.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Elena Fountzilas: Advisory Role: LEO Pharma, Amgen, DEMO. Speaker fees: Roche, Pfizer, AstraZeneca, GSK, Amgen. Stock ownership: GENPREX INC, Deciphera Pharmaceuticals, Inc. Travel grant: Genesis, Pfizer, DEMO and Astra Zeneca. Dr. Henry Hiep Vo reports no relevant conflicts of interest. Dr. Peter Mueller reports no relevant conflicts of interest. Dr. Razelle Kurzrock has the following financial relationships to disclose: Research Funding (Institution): Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Konica Minolta, Grifols, Biologic Dynamics, Boehringer Ingelheim, Medimmune, and Guardant. Consulting role: X-Biotech, Loxo, Biologic Dynamics, Turning Point, TD2, Bicara, and Actuate Therapeutics. Speaker fees: Roche. Ownership interest: IDbyDNA and CureMatch, Inc. Board member: CureMatch and CureMetrix. Dr. Apostolia-Maria Tsimberidou has the following financial relationships to disclose: Research Funding (Institution): OBI Pharma, Parker Institute for Cancer Immunotherapy, Immatics, Tvardi Therapeutics, Tempus, Boston Biomedical, Placon Therapeutics, Karus Therapeutics and Agenus. Consulting or Advisory Role: Vincerx, Diaccurate, BrYet, Avstera, Macrogenics, Bioeclipse, Nex-I.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)