90P - Effect of age on safety and efficacy of novel cancer drugs investigated in early phase clinical trials

Background

Although cancer often develops in advanced age, elderly patients (pts) are still underrepresented in clinical trials, especially phase I trials. Our study aimed to compare safety and efficacy of treatments in early phase clinical trials between younger and elderly pts (aged ≤/>65 years).

Methods

We retrospectively collected clinicopathologic characteristics and treatment outcomes of pts consecutively enrolled in early phase clinical trials at our institution from Jan 2014 to Apr 2021. Toxicity and clinical outcomes were compared between younger and elderly pts.

Results

419 pts were included in the analysis. Median age was 56 years (range 26-84); 107 (26%) pts were older than 65. The most common tumor types were breast (48%), lung cancer (9%), and melanoma (5%). Pts were treated in 64 trials primarily receiving immunotherapy (47%) or targeted agents (46%). Younger pts more frequently received targeted therapies compared to elderly (50% vs 35%; p=0.007). Elderly pts had worse baseline ECOG performance status (PS) (p=0.002), received fewer prior lines (p=0.04), and had fewer metastatic sites (p=0.04). Median follow-up was 20 months (range 1.7-85). Grade ≥3 adverse events were similar in both groups (31% vs 33%; p=0.7), even when treated with combination therapies. Elderly pts had a higher rate of treatment discontinuation due to treatment-related toxicities compared to younger (17% vs 7.9%; p=0.008). The objective response rate (19% vs 25%; p=0.22), disease control rate (48% vs 58%; p=0.07), and median progression-free survival (3.57 vs 5 months; p=0.08) were comparable in both groups. No significant difference in overall survival (OS) was observed by age groups (HR 0.91, 95% CI 0.69-1.19; p=0.47) after multivariate adjustment for ECOG PS, target lesions sum, and Royal Marsden Hospital prognostic score, which conversely were independently associated with OS.

Conclusions

Safety and efficacy of new targeted and immunotherapy drugs in elderly pts enrolled in early phase clinical trials are comparable to younger pts. These data suggest that age should not limit consideration of early phase clinical trials as a treatment option; enrollment of elderly pts should be even more encouraged in the era of precision medicine. Jacopo Uliano and Eleonora Nicolò have equally contributed to this work and share first authorship.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Tarantino: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo. C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli Lilly, Roche, Gilead; Financial Interests, Personal, Advisory Board: MSD, Seagen, AstraZeneca, Daiichi Sankyo. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Personal, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Council, Patient Advocacy Association: Europa Donna; Non-Financial Interests, Personal, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Personal, Invited Speaker, No compensation for this role, This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Personal, Officer, Member of the Advisory Council: EUSOMA. All other authors have declared no conflicts of interest.