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4532 Background: Multiple regimens incorporating tyrosine kinase inhibitors (TKI) or immune checkpoint inhibitors (ICI), either alone or in combination, confer a significant OS benefit in 1L metastatic clear cell RCC. However, guidance for optimal treatment selection in elderly patients remains limited. A network meta-analysis (NMA) was performed to compare the efficacy of 1L treatments for elderly patients with aRCC. Methods: Database search was performed through Pubmed, Embase, Web of Science, and Scopus. Eligible studies were randomized controlled trials (RCTs) evaluating first-line regimens for patients with aRCC older than 65 years old. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Indirect comparisons of available regimens were estimated using a random-effects NMA. Results: 14 RCTs with more than 2,100 patients and 5 RCTs with 1,529 patients were eligible for PFS and OS analyses, respectively. Compared with sunitinib (Sun), the pembrolizumab (Pem) + axitinib (Axi) (HR 0.68, 95% CI 0.48-0.97) and Pem + lenvatinib (Len) (HR 0.61, 95% CI 0.4-0.94) regimens were associated with significantly improved OS. In comparing the TKI-ICI combinations with dual ICI nivolumab (Niv) + ipilimumab (Ipi), no significant OS differences were observed (Pem + Len: HR 0.71, 95% CI 0.40-1.27; Pem + Axi: HR 0.79, 95% CI 0.47-1.34; Avelumab (Ave) + Axi: HR 1.03, 95% CI 0.58-1.85; Niv + cabozantinib [Cab]: HR 1.03, 95% CI 0.57-1.93, using Niv + Ipi as a reference). Pem + Len, Niv + Cab, Pem + Axi, and Cab alone each showed improved PFS over Sun (Table). Among these, Pem + Len showed a PFS advantage compared to Pem + Axi (HR 0.58, 95% CI 0.37-0.91), but no PFS difference compared with the other regimens (vs Niv + Cab: HR 0.63, 95% CI 0.39-1.03; vs Cab alone: HR 0.84, 95% CI 0.40-1.77). Conclusions: Pem + Len and Pem + Axi provided the largest OS benefit in elderly patients for 1L aRCC. Pem + Len showed improved PFS compared with Pem + Axi, but no difference compared with Niv + Cab or Cab alone. Further validation using real-world data is needed to confirm the efficacy and safety of first-line regimens for the geriatric population with aRCC.[Table: see text]

2645 Background: Immune checkpoint blockade (ICB) has emerged as a promising treatment strategy for many solid tumors. Although safe for many patients, ICB causes immune-related adverse events (irAEs) including hepatitis, which may result in morbidity and treatment disruption. Severe hepatitis requires immunosuppression, including corticosteroids and mycophenolate mofetil. We conducted a meta-analysis of clinical trials to investigate the effect of adding ICB to conventional solid tumor therapy on the incidence of hepatitis. Methods: Phase 3 randomized clinical trials (RCTs) comparing ICB and conventional therapy to conventional therapy alone were chosen by database search on PubMed, Embase, Web of Science, and Cochrane Library. The odds ratios [OR] of any-grade and grade ≥3 hepatitis, elevated aspartate aminotransferase (AST), and elevated alanine aminotransferase (ALT) were calculated. Meta-analysis was conducted to determine the incidence of hepatitis, elevated AST, and elevated ALT among patients receiving ICB and those receiving conventional therapy alone. Subgroup analysis based on the mechanism of ICB (Cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] inhibitor, programmed cell death protein 1 [PD-1] inhibitor, and programmed death-ligand 1 [PD-L1] inhibitor) was also conducted. Results: A total of 29 randomized controlled trials (RCTs) enrolling 18,829 participants were analyzed. Incidence of hepatitis was derived from 24 RCTs enrolling 15,183 patients, and incidence of grade ≥3 hepatitis was derived from 22 RCTs enrolling 13,846 patients. Incidence of elevated AST was extracted from 18 RCTs, and incidence of elevated ALT was extracted from 20 RCTs. Addition of ICB to conventional therapy was associated with an increase in incidence of any-grade hepatitis (OR 2.54, 95% confidence interval [CI] 1.82-3.55) and grade ≥3 hepatitis (OR 4.22, 95% CI 2.51-7.11). The addition of ICB was also associated with an increase in incidence of elevated AST (any grade: OR 2.19, 95% CI 1.59-3.03; grade ≥3: OR 3.18, 95% CI 1.85-5.48) and elevated ALT (any grade: OR 2.08, 95% CI 1.47-2.92; grade ≥3: OR 2.41, 95% CI 1.40-4.14). Subgroup analysis based on the mechanism of ICB demonstrated increased incidence of grade ≥3 hepatitis associated with CTLA-4 inhibitor, PD-1 inhibitor, and PD-L1 inhibitor therapy (OR 2.78, 95% CI 1.26-6.14; OR 6.30, 95% CI 2.23-17.78; OR 4.73, 95% CI 1.83-12.23, respectively). No significant difference of heterogeneity was observed among subgroups ( I2= 0%, p = 0.43). Conclusions: Addition of ICB to conventional solid tumor therapy was associated with increased incidence of any-grade and severe hepatitis, and elevations of AST and ALT, regardless of the mechanism of ICB. Clinicians should weigh the risk of liver toxicity when considering addition of ICB therapy in patients with solid tumors.

e18007 Background: Concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) is a standard treatment for locally advanced head and neck cancer (LAHNC) in the definitive setting. Three cycles of 100 mg/m2 CDDP for every three weeks (Q3W) are now recommended but compliance with CCRT is relatively low due to its severe toxicity. Therefore, the potential de-escalation strategies for LAHNC have been discussed to decrease the therapeutic toxicity. Methods: Patients with LAHNC who underwent definitive CCRT with CDDP between 2012 and 2018 at The Cancer Institute Hospital of Japanese Foundation for Cancer Research were analyzed. Patients were classified into two groups based on the planned CDDP dose: (A) 100 mg/m2 and (B) 80 mg/m2 Q3W for three times. One-to-one propensity score matching was performed to minimize bias between two groups. After patients in two groups were matched by using propensity score, the overall survival (OS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), and metastatic recurrence-free survival (MRFS) were analyzed by the Kaplan-Meier method with the Cox proportional hazards model. The follow-up term was set as two years to evaluate the early survival benefit. The dose and density of CDDP and the objective adverse events were also assessed. Results: A total of 304 patients were included with the median age of 62 (Interquartile range [IQR]: 54-67) years. Among them, 249 patients (82%) were male. Patients were treated with 100 mg/m2 CDDP (n = 145) and 80 mg/m2 CDDP (n = 159) regimens. After the propensity score matching, 119 patients were included in each group, respectively. There were no significant differences in baseline characteristics between two propensity-matched cohorts. The median follow-up time was 24 months in each group. Two-year OS was 93.0% (95% confidence interval [CI]: 88.4-97.8) in group A and 94.9% (91.0-99.0) in group B. Two-year RFS was 86.5% (80.6-92.9) in group A and 83.1% (76.6-90.1) in group B, respectively. No significant difference was observed in OS (Hazard ratio [HR] = 1.42, 95% CI: 0.49-4.08, p = 0.52), RFS (HR = 0.81, 95% CI: 0.42-1.57, p = 0.54), LRFS (HR = 0.57, 95% CI: 0.24-1.36, p = 0.20), and MFS (HR = 1.32, 95% CI: 0.52-3.35, p = 0.56). The median cumulative dose of CDDP was significantly higher in group A (300 mg, interquartile range [IQR]: 240-300) than in group B (240 mg, IQR:160-240) but the frequency of hematological, hepatic, renal, electrolytic, and grade 3-5 any adverse events was not significantly different between two groups. Conclusions: Our study showed no survival difference at 2-year follow-up between 100 mg/m2 and 80 mg/m2 CDDP regimens of definitive CCRT for LAHNC. This result could support the tide of the de-escalation strategy in head and neck cancer treatment. Longer follow-up is necessary and further prospective trials comparing CDDP dosage are warranted.