Pawar, Omkar

605 Background: Multiple treatment modalities are available for localized hepatocellular carcinoma (HCC), and current Barcelona Clinic Liver Cancer (BCLC) guidelines recommend ablation for patients with a limited number of small tumors, not amenable to resection or transplantation. However, in recent years, stereotactic body radiation therapy (SBRT) has been increasingly used for localized disease. Patient outcomes based on treatment modality are not well understood. Methods: We conducted a retrospective analysis using the National Cancer Database (NCDB) to identify patients with a history of stage I/II HCC with tumors ≤ 5 cm who had received local therapy with either radiofrequency ablation (RFA) or SBRT between 2006 and 2021. A propensity score matched analysis was conducted accounting for patient demographics, facility region and tumor level characteristics, as well as an inverse probability of treatment weight-adjusted (IPTW) analysis. Overall survival was estimated using the Kaplan-Meier method. Results: We identified 14,516 patients meeting inclusion criteria, including 13,036 who received RFA and 1,480 who received SBRT. Demographic factors associated with receipt of SBRT included age >50 years, female sex, and treatment in the Middle Atlantic and East North Central regions, as well as clinical factors including larger tumor size (>3 to 5 cm), severe fibrosis/cirrhosis, and stage II disease ( p <0.05 for all). Factors associated with receipt of RFA include black race, higher Charlson-Deyo Comorbidity Scores, treatment at a comprehensive cancer program or integrated network cancer program, and treatment in the East South Central, West North Central, West South Central, Mountain, and Pacific Regions ( p <0.05 for all). Median time from diagnosis to treatment initiation was longer for those who received SBRT (66.3 vs 84.6 days, p <0.001). In a propensity matched analysis, mOS was 45.1 months for those receiving RFA vs 30.8 months for those receiving SBRT ( p <0.001). An IPTW analysis showed similar survival benefit with RFA over SBRT (mOS 51.0 vs 30.5 months, p <0.001). This OS benefit was observed in subset of patients with tumors <3cm in size. Conclusions: In this propensity matched analysis controlling for relevant patient and tumor factors, RFA was associated with improved survival. Prospective studies will be important to further analyze differences in patient outcomes.

PURPOSE Limited treatment options exist for patients with locally advanced or metastatic biliary tract cancers (BTCs). Recently, several clinical trials provided preliminary evidence for human epidermal growth factor receptor 2 (HER2) as a new target for patients with HER2-expressing BTC. We conducted a systematic review and pooled analysis of the safety and efficacy of anti-HER2 agents in patients with advanced BTCs. METHODS A comprehensive search of PubMed/MEDLINE and EMBASE was performed to identify phase I, II, or III clinical trials published between January 2019 and March 2024 that evaluated anti-HER2 therapy in locally advanced or metastatic BTC. Participant data included in the analysis were from trials evaluating the efficacy and safety of various anti-HER2 agents. The primary end points included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). The secondary end points included incidence of treatment-related adverse events (TRAEs), rate of treatment discontinuation, and death. RESULTS The analysis included 368 patients from eight publications diagnosed with advanced BTC. Patients were treated with several anti-HER2 agents including zanidatamab, pertuzumab plus trastuzumab, tucatinib plus trastuzumab, trastuzumab deruxtecan, trastuzumab plus chemotherapy, trastuzumab-pkrb plus chemotherapy, and neratinib. The pooled ORR and DCR were 34% (95% CI, 24 to 44) and 64% (95% CI, 51 to 77), respectively. The pooled weighted PFS and median overall survival were 4.8 and 9.4 months, respectively. The pooled duration of response for the reporting trials was 5.0 months. In the study cohort, 82.6% of patients experienced any adverse event and 32.1% experienced a grade 3-4 adverse event. Only 5.7% of the patients discontinued treatment secondary to TRAEs. CONCLUSION In patients with HER2-expressing BTCs, anti-HER2 therapies are viable options, particularly in the second-line setting.

639 Background: Limited treatment options exist for patients with locally advanced or metastatic biliary tract cancers (BTCs). Recently, several clinical trials provided preliminary evidence for human epidermal growth factor receptor-2 (HER2) as a new target for patients with HER2 expressing BTC. We conducted a systematic review and pooled analysis of the safety and efficacy of anti-HER2 agents in patients with advanced BTC. Methods: A comprehensive search of PubMed/MEDLINE and EMBASE was performed to identify phase 1, 2, or 3 clinical trials published between January 2019 and March 2024 that evaluated anti-HER2 therapy in locally advanced or metastatic BTC. Primary endpoints included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Secondary endpoints included the incidence of treatment-related adverse events (TRAEs), rate of treatment discontinuation, and death. Forest plots were generated to summarize the results and demonstrate the effect size estimates for each study, along with their confidence intervals and the pooled estimate from the random-effects model. The random-effects models were configured to use the Restricted Maximum Likelihood method for estimating between-study variance for all analyses. Results: After excluding duplicate and irrelevant articles, data extraction and analysis were performed on eight selected clinical trials. The analysis included 368 patients with a median age of 64 (range 49-68), with 55% being female. Patients were treated with several anti-HER2 agents, including zanidatamab, pertuzumab plus trastuzumab, tucatinib plus trastuzumab, trastuzumab deruxtecan, trastuzumab plus chemotherapy, trastuzumab-pkrb plus chemotherapy and neratinib. The pooled ORR and DCR were 34% (95% CI 24-44) and 64% (95% CI 51-77) respectively. The pooled weighted PFS and median OS survival were 4.8 and 9.4 months, respectively. The pooled duration of response was 5.0 months. In our subset analysis, which included only patients who had received ≥1 prior therapy, the pooled ORR was 30% (95% CI 22-39), the pooled DCR was 62% (95% CI 48-75), and the pooled median PFS was 4.4 months. In the study cohort, 82.6% of patients experienced any adverse event, and 32.1% experienced a grade 3-4 adverse event. Only 5.7% of the patients discontinued treatment secondary to TRAEs. Conclusions: In patients with HER2 expressing BTCs, anti-HER2 therapies demonstrated preliminary signals of efficacy with manageable toxicities, particularly in the second-line setting.