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Toxicity and antitumor activity of novel agents in elderly patients with cancer included in phase 1 studies

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Summary

Introduction The number of cancer cases among the elderly continue to increase as the worldwide population ages. This patient subset is underrepresented in clinical trials, partly because of unresolved uncertainties about age-associated tolerabilities and antitumor activities. We reviewed phase 1 trial data to study tolerance and efficacy of novel agents used for treatment of elderly patients with cancer. Methods Data from 773 consecutive evaluable patients in 85 phase 1 clinical trials (2008–2016) at START Madrid-CIOCC were analyzed according to age, with respect to objective response, survival, and toxicity. Results The mean age was 58.7 (range: 18–87) years; 260 (33.6%) patients were >65 y (elderly group). One hundred thirty-seven (17.8%) patients received immunotherapy drugs, 308 (39.8%) received targeted agents, and 328 (42.4%) received chemotherapy. No statistically significant differences in overall survival, objective response, or severe toxicity rates were found according to treatment type. Similar toxicities and clinical activities were found between the two age subgroups; 18.8% of the elderly and 20.7% of the younger patients experienced severe hematological toxicity (p=0.5), and 30.2% and 32.7%, respectively, experienced severe non-hematological toxicity (p=0.4). Regarding antitumor activity, 12.4% of the elderly and 15% of the younger patients achieved objective responses (p=0.41). There were no significant between-group differences in overall survival (9.7 versus 11.5 months, respectively, p=0.1) or progression-free survival (2.3 versus 2.2 months, respectively, p=0.7). Conclusions This retrospective study found that elderly and younger populations had comparable antitumor activities and toxicity profiles. These results support including elderly patients with cancer in early-phase trials.

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Acknowledgments

None to report.

Funding

This work was supported by START Madrid at CIOCC as a Ph.D. studentship.

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Authors and Affiliations

  1. START Madrid-HM CIOCC, Centro Integral Oncológico Clara Campal, Hospital Universitario HM Sanchinarro, Calle Oña, 10. 28050, Madrid, Spain

    Geriletu Ao, Maria de Miguel, Ana Gomes, Runhan Liu, Valentina Boni, Irene Moreno & Emiliano Calvo

  2. Departamento de Matemática Aplicada y Estadística, San Pablo CEU University. Calle Julián Romea, 18. 28003, Madrid, Spain

    José Miguel Cárdenas

  3. Centro Integral, Oncológico Clara Campal. Hospital Universitario HM Sanchinarro. Calle Oña, 10. 28050, Madrid, Spain

    Antonio Cubillo & Lisardo Ugidos

  4. Facultad de Medicina, Departamento de Ciencias Médicas Clínicas, Universidad CEU San Pablo. Plaza Montepríncipe, 1D, 28668, Alcorcón, Madrid, Spain

    Antonio Cubillo

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  1. Geriletu Ao
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Contributions

Conception and design: G.A., L.U., M.M., E.C. Writing, review, and/or revision of manuscript: G. A., M.M., A.G., L.U., A.C., R.L, V.B., I.M., E.C. Acquisition of data: G.A., L.U. Analysis and interpretation of data: G.A., L.U., M.M., J.M.C., E.C.

Corresponding author

Correspondence to Emiliano Calvo.

Ethics declarations

Ethical approval and consent to participate

This study complies with the guidelines for human studies and was performed ethically in accordance with the World Medical Association Declaration of Helsinki. The study was exempt from ethical committee approval because the work was a review of different Pharma-sponsored phase 1 clinical trials that were formally approved by the respective ethics committees and the Spanish regulatory agency. The clinical studies data that we used to perform our analyses were properly anonymized and complied with the laws of Spain relevant to protection of personal data. Informed consent was obtained from each patient at the time of original data collection.

Informed consent

Not applicable. This study was a pooled retrospective analysis of associations of characteristics of patients. Per standard requirements, no informed consent was required.

Research involving human and animals participants

Not applicable. No specific research involving human participants and/or animals is applicable because this study was a retrospective analysis of patients treated during previously published phase 1 clinical trials.

Disclosures of potential conflicts of interest

  • • Geriletu Ao declares no potential conflicts of interest

  • • Maria de Miguel reports research funding from MSD, Pharmamar, Roche, Novartis, Abbvie, Array, Eisai, and Sanofi. Speaker´s Bureau: MSD, Janssen, Roche.

  • • Ana Gomes declares no potential conflicts of interest

  • • Runhan Liu declares no potential conflicts of interest

  • • Valentina Boni reports employment at START Madrid-CIOCC, Hm Hospitales Sanchinarro. Consulting or advisory roles at Puma Biotechnology, Ideaya Biosciences, Loxo Therapeutics, CytomX Therapeutics, Guidepoint, Oncoart. Institutional financial support for clinical trials from Abbvie, ACEO, Adaptaimmune, Amcure, AMGEN, AstraZeneca, BMS, Cytomx, GSK, Genentech/Roche, H3, Incyte, Janssen, Kura, Lilly, Loxo, Nektar, Macrogenics, Menarini, Merck, Merus, Nanobiotix, Novartis, Pfizer, PharmaMar, Principia, PUMA, Sanofi, Taiho, Tesaro, BeiGene, Transgene, Takeda, Incyte, Innovio, MSD, PsiOxus, Seattle Genetics, Mersana, GSK, Daiichi, Nektar, Astellas, ORCA, Boston Therapeutics, Dynavax, DebioPharm, Boehringen Ingelheim, Regeneron, Millenium, Synthon, Spectrum, Rigontec, Zenith. Memberships at SEOM, ESMO, ASCO, SOLTI (scientific committee member), GETHI.

  • • Irene Moreno reports research funding from Abbvie, Astellas, BMS, Pharmamar, Kyowa and Symphogen. Speaker´s Bureau: MSD.

  • • José Miguel Cárdenas declares no potential conflicts of interest.

  • • Lisardo Ugidos reports advisory role for Astra Zeneca.

  • • Antonio Cubillo reports no potential conflicts of interest.

  • • Emiliano Calvo reports honoraria or consultation fees from Astellas, Novartis, Nanobiotix, Pfizer, Janssen-Cilag, GLG, PsiOxus Therapeutics, Merck, Medscape, BMS, Gilead, Seattle Genetics, Pierre Fabre, Boehringer Ingelheim, Cerulean Pharma, EUSA, Gehrmann Consulting, AstraZeneca, Roche, Guidepoint, Servier, Celgene, Abbvie, Amcure, OncoDNA, Alkermes. Director of Clinical Research, START Madrid and Director of Clinical Research at HM Hospitals Group, Madrid. Stocks or ownership in START, Oncoart Associated, International Cancer Consultants. No licensing fees or royalties. Direct research funding as project lead from Novartis, AstraZeneca, Beigene. Institutional financial support for clinical trials from Abbvie, ACEO, Adaptaimmune, Amcure, AMGEN, AstraZeneca, BMS, Cytomx, GSK, Genentech/Roche, H3, Incyte, Janssen, Kura, Lilly, Loxo, Nektar, Macrogenics, Menarini, Merck, Merus, Nanobiotix, Novartis, Pfizer, PharmaMar, Principia, PUMA, Sanofi, Taiho, Tesaro, BeiGene, Transgene, Takeda, Incyte, Innovio, MSD, PsiOxus, Seattle Genetics, Mersana, GSK, Daiichi, Nektar, Astellas, ORCA, Boston Therapeutics, Dynavax, DebioPharm, Boehringer Ingelheim, Regeneron, Millenium, Synthon, Spectrum, Rigontec. Member of scientific board at PsiOxus, non-financial interest. Founder and president of non-profit foundation INTHEOS (Investigational Therapeutics in Oncological Sciences), medical society. Memberships in SEOM, EORTC, ESMO, ASCO. Other relationships: HM Hospitals Group and START, Program of Early Phase Clinical Drug Development in Oncology; Employed as Medical Oncologist, Director, Clinical Research. Methods in Clinical Cancer Research (MCCR) Workshop, Zeist, Netherlands (Joint ECCO-AACR-EORTC-ESMO Workshop on Methods in Clinical Cancer, Research), Co-director.

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Ao, G., de Miguel, M., Gomes, A. et al. Toxicity and antitumor activity of novel agents in elderly patients with cancer included in phase 1 studies. Invest New Drugs 39, 1694–1701 (2021). https://doi.org/10.1007/s10637-021-01150-1

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