Abstract
1625 Background: Older adults aged ≥65 with advanced cancer are underrepresented in treatment trials. This gap limits informed decision-making regarding the dose and tolerability of proposed therapies. Standard chemotherapy is associated with >50% serious adverse event rate among older adults, with frequent dose reduction and early treatment discontinuation. A "start low, go slow" (SLGS) approach begins systemic therapy at lower-than-standard doses and increases the dose if well-tolerated. This alternative dosing strategy has shown value in minimizing adverse events and functional decline without compromising the overall effectiveness of treatments. We conducted the first systematic review and meta-analysis of SLGS effectiveness among older adults across advanced cancers. Methods: This review, was registered with PROSPERO and adhered to PRISMA criteria, covering PubMed, Journal of Geriatric Oncology and EMBASE from January 2000 until December 15, 2024. Eligible study designs were randomized controlled trials, retrospective trials, and non-randomized clinical trials with patients with advanced cancers who underwent systemic therapy. We reported all studies that studied the SLGS approach. Our studied outcomes were overall survival (OS), progression-free survival (PFS), treatment discontinuation, and toxicity. Data extraction included author, patient, cancer type, treatment, and survival outcomes. A meta-analysis using fixed effects and risk ratios (RR) was performed when sufficient data was available; significant outcomes had α<0.05. Results: Our search identified 13 studies testing SLGS strategies in oncology, including 3,508 patients, with a median age 63-78 years. The -represented cancers included colorectal (6 studies, 3059 patients total), lung (2 studies, 113 pts), chronic myeloid leukemia (2 studies, 127 pts), non-Hodgkin lymphoma (1 study, 45 pts), and prostate (2 studies, 164 pts) cancers. Ten (77%) studies assessed OS and PFS. Five studies (39%) compared SLGS against standard doses, finding no significant differences in PFS and OS across all trials. Dose escalation rates for SLGS ranged from 5% to 60%. The ability to complete planned cycles was higher with SLGS compared to standard dose (1 study, 43% vs 26%, p=0.04). Treatment discontinuation was not different for SLGL vs. standard dose (5 studies, meta-analysis RR 1.07, 95% CI 0.90-1.27, p=0.42). Toxicity ranged from 5% to 89% across studies; SLGS had lower grade ≥3 adverse events compared to standard dose (4 studies, meta-analysis RR 0.88, 95% CI 0.80-0.94, p < 0.001). Conclusions: This is the first systematic review and meta-analysis analyzing the SLGS approach to systemic therapy dosing in older adults with advanced cancer. Compared to standard-dose systemic therapy, older adults pursuing a SLGS strategy had greater completion of planned cycles, reduced toxicity, and similar survival.
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