Effect of Age on Safety and Efficacy of Novel Cancer Drugs Investigated in Early-Phase Clinical Trials

24 Pages Posted: 17 May 2024

See all articles by Eleonora Nicolò

Eleonora Nicolò

Cornell University - Weill Cornell Medicine

Sara Gandini

European Institute of Oncology (IEO) IRCCS

Federica Giugliano

affiliation not provided to SSRN

Jacopo Uliano

affiliation not provided to SSRN

Oriana D’Ecclesiis

affiliation not provided to SSRN

Stefania Morganti

Harvard University - Dana-Farber Cancer Institute

Emanuela Ferraro

Memorial Sloan Kettering Cancer Center

Dario Trapani

European Institute of Oncology (IEO) IRCCS

Paolo Tarantino

Harvard University - Dana-Farber Cancer Institute

Paola Zagami

affiliation not provided to SSRN

Laura Boldrini

affiliation not provided to SSRN

Irene Caramella

affiliation not provided to SSRN

Ambra Carnevale Schianca

affiliation not provided to SSRN

Massimo Cristofanilli

Cornell University - Weill Cornell Medicine

Marzia Adelia Locatelli

affiliation not provided to SSRN

Angela Esposito

affiliation not provided to SSRN

Carmen Belli

affiliation not provided to SSRN

Ida Minchella

affiliation not provided to SSRN

Carmen Criscitiello

affiliation not provided to SSRN

Antonio Marra

affiliation not provided to SSRN

Giuseppe Curigliano

European Institute of Oncology (IEO) IRCCS - Division of New Drugs and Early Drug Development for Innovative Therapies

Abstract

BackgroundElderly patients are underrepresented in clinical trials, particularly in early-phase studies. Our study assessed the safety and efficacy of novel anti-cancer treatments investigated in early-phase clinical trials, comparing outcomes between younger and elderly patients.MethodsThis retrospective study analyzed data from patients enrolled in phase I/II trials at our center between January 2014 and April 2021. We evaluated clinicopathologic characteristics, toxicity, and clinical efficacy, categorizing patients into younger (≤65 years) and elderly (>65 years) groups.Results419 patients were included with a median age of 56 years. Among these, 107 (26%) were older than 65 years. Predominant cancers included breast (48%), lung (10%), and melanoma (5%). Patients were treated in 64 trials, predominantly receiving immunotherapy-based (47%) or targeted therapy-based (45%) treatment. Elderly presented with poorer ECOG performance status (P=0.001) and had fewer prior therapy lines (P=0.01) than younger patients. Grade ≥3 adverse events(AEs) were similar across age groups (31% younger vs 33% elderly; P=0.7), including in combination therapy scenarios. However, elderly patients experienced more AEs with antibody-drug conjugates compared to younger counterparts (56% vs 14%, P=0.036) and were more likely to discontinue treatment due to toxicity (17% vs 8%; P=0.008).Response rates, progression-free survival, and overall survival showed no significant age-related differences.ConclusionsOur findings suggest that elderly exhibit comparable safety and efficacy outcomes to younger patients in early-phase clinical trials for new cancer drugs. This underscores the importance of including elderly patients in phase I/II trials to ensure the generalizability of study results and mitigate age-related disparities in cancer treatment access.

Note:
Funding declaration: : EN was supported by an American-Italian Cancer Foundation Post-Doctoral Research Fellowship. AM is supported by the European Society for Medical Oncology José Baselga Fellowship for Clinician Scientists founded by AstraZeneca (2023–2025). SM acknowledges the support from the Italian Association for Cancer Research (AIRC) and Gianni Bonadonna Foundation.

Conflict of Interests: SM reports expenses reimbursement from Menarini/Stemline and AstraZeneca. PT discloses research funding (to institution) from AstraZeneca and consultancy/advisory role for AstraZeneca, Daiichi Sankyo, Gilead, Novartis and Lilly. MC reports personal fees from Lilly, Sermonix, Data Genomics, Foundation Medicine, Guardant Health, Celcuity, Iylon, and Ellipses and grants and personal fees from Pfizer, AZ and Menarini, all outside the submitted work. CC reports consultancy/advisory role/speaker bureau: AstraZeneca, Daiichi Sankyo, MSD, Gilead, Lilly, Roche, Pfizer, Novartis and Seagen, all outside the submitted work. AM has received honoraria as a consultant, advisor or speaker from Roche and Menarini/Stemline, and has received support for accommodation and travel from AstraZeneca, all outside the submitted work. AE reports speaker bureau: Daiichi Sankyo, Novartis, all outside the submitted work. GC reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events: Lilly, Pfizer, Relay, Gilead, Novartis; Consulting fees: BMS, Roche, Pfizer, Novartis, Lilly, Astra Zeneca, Daichii Sankyo, Merck, Seagen, Ellipsis, Gilead, Menarini; Grants or contracts: Merck; Support for attending meetings and/or travel: Daichii Sankyo. Institutional research funding for conducting Phase 1 and 2 clinical trials: Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, BMS, Merck Serono, Merck Sharp Dohme, Janssen-Cilag, Philogen, Bayer, Medivation, Medimmune. All outside the submitted work. No other potential conflicts of interest are reported.

Ethical Approval: The study protocol was approved by the institutional review board and local ethics committee (approval number UID 3560) and was conducted in accordance with the Declaration of Helsinki.

Keywords: Cancer, solid tumors, age, elderly, phase I, early-phase clinical trial, new drugs, adverse events, Survival, outcome

Suggested Citation

Nicolò, Eleonora and Gandini, Sara and Giugliano, Federica and Uliano, Jacopo and D’Ecclesiis, Oriana and Morganti, Stefania and Ferraro, Emanuela and Trapani, Dario and Tarantino, Paolo and Zagami, Paola and Boldrini, Laura and Caramella, Irene and Schianca, Ambra Carnevale and Cristofanilli, Massimo and Locatelli, Marzia Adelia and Esposito, Angela and Belli, Carmen and Minchella, Ida and Criscitiello, Carmen and Marra, Antonio and Curigliano, Giuseppe, Effect of Age on Safety and Efficacy of Novel Cancer Drugs Investigated in Early-Phase Clinical Trials. Available at SSRN: https://ssrn.com/abstract=4821673 or http://dx.doi.org/10.2139/ssrn.4821673

Eleonora Nicolò

Cornell University - Weill Cornell Medicine ( email )

1300 York Avenue
New York, NY 10065
United States

Sara Gandini

European Institute of Oncology (IEO) IRCCS ( email )

via Adamello 16
Milano, 20139
Italy

Federica Giugliano

affiliation not provided to SSRN ( email )

No Address Available

Jacopo Uliano

affiliation not provided to SSRN ( email )

No Address Available

Oriana D’Ecclesiis

affiliation not provided to SSRN ( email )

No Address Available

Stefania Morganti

Harvard University - Dana-Farber Cancer Institute ( email )

Boston, MA
United States

Emanuela Ferraro

Memorial Sloan Kettering Cancer Center ( email )

Dario Trapani

European Institute of Oncology (IEO) IRCCS ( email )

Paolo Tarantino

Harvard University - Dana-Farber Cancer Institute ( email )

450 Brookline Avenue
Boston, MA 02215
United States

Paola Zagami

affiliation not provided to SSRN ( email )

No Address Available

Laura Boldrini

affiliation not provided to SSRN ( email )

No Address Available

Irene Caramella

affiliation not provided to SSRN ( email )

No Address Available

Ambra Carnevale Schianca

affiliation not provided to SSRN ( email )

No Address Available

Massimo Cristofanilli

Cornell University - Weill Cornell Medicine ( email )

New York, NY
United States

Marzia Adelia Locatelli

affiliation not provided to SSRN ( email )

No Address Available

Angela Esposito

affiliation not provided to SSRN ( email )

No Address Available

Carmen Belli

affiliation not provided to SSRN

No Address Available

Ida Minchella

affiliation not provided to SSRN ( email )

No Address Available

Carmen Criscitiello

affiliation not provided to SSRN ( email )

No Address Available

Antonio Marra

affiliation not provided to SSRN ( email )

No Address Available

Giuseppe Curigliano (Contact Author)

European Institute of Oncology (IEO) IRCCS - Division of New Drugs and Early Drug Development for Innovative Therapies ( email )

Italy

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