Impact of geriatrician-implemented Interventions on chemotherapy (CT) delivery in vulnerable elderly patients with early or advanced solid tumors: The GIVE trial

BackgroundFrail older adults with cancer have a higher risk for treatment toxicities and adverse health outcomes. Comprehensive geriatric assessment (CGA) is a standard of care to detect and reduce health problems leading to frailty. We examined whether CGA-based interventions can impact optimal CT delivery in a cohort of vulnerable older patients with cancer.MethodsThis multicenter randomized trial enrolled patients aged ≥70 years, with early or advanced solid tumors considered for CT, presenting with ≥1 deficit on CGA and/or ≥1 grade 3-4 comorbidity on Cumulative Illness Rating Scale- Geriatric (CIRS-G). Patients were randomized 2:1 to routine oncological care plus geriatric intervention (Arm A) or routine oncological care (Arm B). The primary outcome was to compare the proportion of patients achieving a CT relative dose intensity (RDI) of ≥85% between Arm A and Arm B. Secondary outcomes included rates of hospitalizations and treatment-related toxicity.ResultsWe enrolled 225 patients (135 in Arm A and 90 in Arm B). The median age was 77 (range 70-91) years, 57% were women, 85% had ECOG performance status 0-1, 63% had metastatic disease. Most patients had gastrointestinal (51%) or breast cancer (15%). The median number of geriatric assessment impaired domains was 3 (range 1-7). Nearly 60% of patients in both arms received an upfront CT dose reduction, with the median reduced dose being 75% of the full dose. The median RDI did not significantly differ between the study arms (77% [range 2%-100%] in Arm A, and 74% [range 6%-100%] in Arm B, respectively; p=0.423). Similarly, we observed no differences in the risk of RDI<85%, and the rate of hospitalization. A lower proportion of patients receiving a geriatric intervention had grade 1–4 toxic effects (76% in Arm A versus 88% in Arm B; p=0.032).ConclusionsIn this study, geriatric interventions did not improve the optimal CT dose delivery in older vulnerable patients; however, they were associated with reduced toxic effects from CT. These results may have been influenced by the high proportion of patients receiving an upfront CT dose reduction. Research is needed on the effects of CGA on CT efficacy in this cohort.Clinical trial identificationNCT02785887.Legal entity responsible for the studyAzienda USL4, Prato.FundingAzienda USL4, Prato.DisclosureE. Risi: Financial Interests, Institutional, Invited Speaker: Eisai, Lilly, Gilead, Daiichi Sankyo; Financial Interests, Institutional, Other: Roche, Pfizer, Gilead. A. Brunello: Financial Interests, Institutional, Speaker, Consultant, Advisor: Boehringer Ingelheim, Deciphera, GSK; Financial Interests, Institutional, Other: PharmaMar. F. Bergamo: Financial Interests, Personal, Invited Speaker: Lilly, BMS, MSD, EISAI, Bayer, Amgen; Financial Interests, Personal, Advisory Board: Servier, AAA; Other, Other, congress: Bayer, Ipsen, AAA. G.G. Baldi: Financial Interests, Institutional, Speaker, Consultant, Advisor: Eli Lilly, PharmaMar, AboutEvents, Boehringer Ingelheim, GSK, Merck Sharp & Dome, Eisai; Financial Interests, Institutional, Other: Novartis, PharmaMar, Eli Lilly; Financial Interests, Institutional, Advisory Board: PharmaMar, Eli Lilly, GSK, Merck Sharp & Dome, Boehringer Ingelheim. L. Malorni: Financial Interests, Personal, Invited Speaker: Pfizer, Lilly, Novartis, Menarini; Financial Interests, Personal, Advisory Board: Lilly, Seagen, Roche, Menarini, Pfizer; Financial Interests, Institutional, Research Grant: Pfizer, Novartis; Financial Interests, Personal, Steering Committee Member: Novartis; Non-Financial Interests, Institutional, Product Samples: Biovica International; Other, Other, Principal investigator in one clinical trialco-Principal Investigator in one clinical trial: International Breast Cancer Study Group (IBCSG). N.M.L. Battisti: Financial Interests, Institutional, Advisory Board: Pfizer, Abbott, Sanofi, Astellas; Financial Interests, Institutional, Other: Exact Sciences, Pfizer, Lilly, Novartis; Financial Interests, Institutional, Speaker, Consultant, Advisor: Pfizer, AbbVie, Roche, Sanofi, Novartis, Servier, Gilead, AstraZeneca, Lilly. L. Biganzoli: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, Gilead, Sanofi, Seattle Genetics, Exact Sciences, Amgen, Boehringer-Ingelheim, Pierre Fabre, Menarini; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Roche; Financial Interests, Institutional, Research Grant: Celgene, Genomic Health, Novartis; Non-Financial Interests, Member of Board of Directors: SIOG. All other authors have declared no conflicts of interest.