Gallbladder Cancer Research Articles

Overall survival outcomes of phase II GECCOR-GB trial, a multicentre trial of adjuvant adjuvant gemcitabine plus cisplatin (GC) and capecitabine with concurrent capecitabine radiotherapy (Cape-RT) for operated gallbladder cancer (GBC).

4124 Background: The optimal adjuvant treatment for gallbladder cancer (GBC) after surgery remains unclear. We previously reported 1 year of disease-free survival (DFS) of adjuvant gemcitabine plus cisplatin (GC) or capecitabine with concurrent capecitabine radiotherapy (Cape-RT). Here, we present the secondary endpoint of the 3-year outcomes of the GECCOR-GB study. Methods: We conducted a multicenter, open-label, non-comparative randomized phase II trial of adjuvant GC or Cape-RT in patients with resected GBC. Patients were randomized 1:1 to receive either GC (gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 6 cycles) or Cape-RT arm {Capecitabine 1000 mg/m2 BD on days 1–14, q 3 weeks for 2-4 cycles followed by chemoradiation (RT: 45 Gy over 25 fractions concurrent with capecitabine: 825 mg/m2 BD) followed by 2-4 cycles of capecitabine for a total of 6 cycles}. The primary endpoint was DFS, and the secondary endpoints were overall survival (OS), safety, and treatment completion rates. Results: We enrolled 90 patients at 3 centers in India between May 2019 and February 2022 and randomly assigned 45 patients to each arm. In the GC arm, the median age of patients was 56 (33–72) years, and 23 (51%) patients were in stage II. While in the cape-RT arm, the median age was 55 (26–69) years, with 27 (60%) patients in stage II. The 3-year DFS was 54.3% in the GC arm and 70.7% in the Cape-RT arm, respectively. The 3-year OS was 75% in the GC arm and 73% in the Cape-RT arm, respectively. The 3-year OS in stage II patients (n = 23) in the GC arm was 91.3%, while in the cape-RT arm (n = 27), it was 91.9%. Median OS in stage III patients (n = 22) was 39.1 (95% CI, 33.4–44.6) months in the GC arm, while in the cape-RT (n = 18), it was 23.2 (95% CI, 7.0–39.4) months. Conclusions: Adjuvant GC arm patients, especially those in stage III, had encouraging OS at 3 years, while both GC and adjuvant Cape-RT arms had excellent 3-year OS, reaching more than 90% in patients with stage II-operated GBC. Further studies are needed to compare and validate these findings for GBC patients. GECCOR-GBwas led by Tata Memorial Hospital (TMC), Mumbai. Clinical trial information: CTRI/2019/05/019323.

The safety and efficacy of ivonescimab in combination with chemotherapy as first-line treatment for advanced biliary tract cancer.

4095 Background: Despite that PD-1/L1 inhibitors combined with chemotherapy have been approved as first-line(1L) treatment for advanced biliary tract cancer (BTC), the overall survival benefit remains limited, particularly for patients with gallbladder cancer. Ivonescimab, a tetrameric bispecific antibody targeting PD-1 and VEGF, has the potential to produce complementary and synergistic anti-tumor effects through both pathways. This study aimed to evaluate the safety and efficacy of ivonescimab in combination with chemotherapy in advanced BTC. Methods: This was an open-label, multi-center phase II study in patients with unresectable locally advanced and metastatic BTC. Ivonescimab was administered every 3 weeks for up to 8 cycles, along with gemcitabine and cis-platinum. After that, ivonescimab monotherapy was given until disease progression or unacceptable toxicity. The primary endpoints were safety and objective response rate (ORR) by RECIST v1.1. Secondary endpoints included duration of response (DoR), disease control rate (DCR), time-to-response (TTR), progression-free survival (PFS), and overall survival (OS). Results: As of Nov 26, 2023, a total of 22 pts with advanced BTC were enrolled in the study. The median age was 65.0 years (range, 47-75), 81.8% of patients had ECOG of 1. All patients had initially unresectable disease status, 54.5% of patients had intrahepatic cholangiocarcinoma, 4.5% of patients had extrahepatic cholangiocarcinoma and 40.9% of patients had gallbladder cancer at baseline. The median follow-up time was 10.7 months, and the median exposure time of ivonescimab was 7.2 months. A total of 86.4% (19/22) of patients experienced at least one grade 3 or higher treatment-related adverse event (TRAE), but none led to discontinuation treatment or death. The most common grade 3/4 TRAEs with a frequency of at least 10% included white blood cell count decreased (50.0%), neutrophil count decreased (50.0%), anemia (40.9%), platelet count decreased (22.7%), and hypertension (13.6%). The ORR by investigator assessment was 63.6% (14/22) regardless of PD-L1 status, with an ORR of 77.8% (7/9) for gallbladder cancer patients specifically. The DCR was 100% (22/22). The median PFS was 8.5 months (95% CI, 6.8-9.9), with a 6-month PFS rate of 84.2% (95% CI, 58.7-94.6). The median OS was 16.8 months (95% CI, 9.8- NE), with a 9-month OS rate of 81.8% (95% CI, 58.5-92.8). Conclusions: Ivonescimab combined with chemotherapy as 1L treatment demonstrated promising efficacy in pts with advanced BTC. Further trials to validate the efficacy and safety are warranted. Clinical trial information: NCT05214482 .

Laparoscopic versus open surgery in treating patients with gallbladder cancer: a systematic review and meta-analysis.

Concerns over the security of laparoscopic radical operation for gallbladder cancer (GBC) persist. This systematic review and meta-analysis attempted to compare the safety and efficacy of laparoscopic surgery (LS) versus open surgery (OS) in the treatment of GBC. The PubMed, EMBASE, and Web of Science were searched from inception to July 18, 2022. Literature search, quality assessment, and data extraction were completed independently and in duplicate. Effect-size estimates expressed as weighted mean difference (WMD) or odds ratio (OR) with 95% confidence interval (CI) were derived under the random-effects model. A total of 27 independent studies including 2,868 participants were meta-analyzed. Significance was noted for intraoperative blood loss (WMD: -117.194, 95% CI: -170.188 to 64.201, P<0.001), harvested lymph nodes (WMD: -1.023, 95% CI: -1.776 to -0.269, P=0.008), postoperative hospital stay (WMD: -3.555, 95% CI: -4.509 to -2.601, P<0.001), postoperative morbidity (OR: 0.596, 95% CI: 0.407 to 0.871, P=0.008), overall survival rate at 2-year (OR: 1.524, 95% CI: 1.143 to 2.031, P=0.004), T2 survival at 1-year (OR: 1.799, 95% CI: 1.777 to 2.749, P<0.01) and 2-year (OR: 2.026, 95% CI: 1.392 to 2.949, P<0.001), as well as T3 survival at 1-year (OR: 2.669, 95% CI: 1.564 to 4.555, P<0.001) and 2-year (OR: 2.300, 95% CI: 1.308 to 4.046, P=0.004). Subgroup analyses revealed that ethnicity, incidental GBC, sample size, and follow-up period were possible sources of heterogeneity. There was a low probability of publication bias for all outcomes except postoperative morbidity. Our findings indicated that LS statistically had better 2-year survival rates, less intraoperative bleeding, shorter hospitalization times, and lower rates of complications than OS. However, the superiority and even the safety of LS still remain an open question due to the impact of incidental GBC, unaccounted heterogeneity, publication bias, lymph node dissection, and port-site metastasis.

Cadonilimab in combined with gemcitabine and cisplatin in advanced biliary tract cancer (BicureX): A phase II, single-arm clinical trial.

e16158 Background: PD-1 or PD-L1 inhibitors plus chemotherapy as the first-line treatment has been proven to be effective in improving the prognosis of advanced biliary tract cancer (BTC) patients. However, there is still considerable demand for further improvement of BTC patients’ prognosis. This trial aims to evaluate the efficacy and safety of Cadonilimab (PD-1/CTLA-4, a bi-specific antibody) plus gemcitabine and cisplatin for patients with advanced BTC in first -line treatment. Methods: In this phase II, single-arm trial, we will enroll 65 patients with previously untreated, unresectable, locally advanced or metastatic BTC, including intrahepatic or extrahepatic cholangiocarcinoma (ICC/ECC) and gallbladder carcinoma (GBC). Participants received Cadonilimab (10 mg/kg, days 1, every three weeks) plus gemcitabine (1000 mg/m2, days 1, 8, Q3W), and cisplatin (25 mg/m2, days 1, 8, Q3W) for up to eight cycles, followed by Cadonilimab (10 mg/kg, days 1, Q3W) until disease progression or unacceptable toxicity. Treatment response was evaluated with image-based assessment according to response evaluation criteria insolid tumors (RECIST) version 1.1. by two experienced experts and further explored multiple methods, such as 3D visualisation and Spectral computed tomography Scan. The primary endpoint was the objective response rate (ORR); the secondary endpoints are disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints included associations between response, molecular characteristics, and the immune microenvironment. Results: Between June 30, and January 31, 2024, a total of 30 patients have undergone at least one imaging evaluation. 66.7% of these patients were diagnosed with ICC, 23.3% with GBC, and 10% with ECC. The mean age was 58.4 years, and 60% of the patients were male. 24 (80%) patients had metastasis. Among them, 1 (3.3%) patient acheived complete response (CR), 15 (50%) patients had partial response (PR) and 8 (26.7%) patients presented with stable disease (SD). The ORR was 53.3% and the DCR was 80%. The most common treatment-related adverse events (TRAEs) of any grade were rash (80%) and anaemia (76.7%). Grade 3 TRAEs were observed in 66.7% of the patients. The most frequent grade 3 TRAEs were anaemia (33.3%), and leukocytopenia (33.3%). No grade 4 or 5 events were observed. All patients were microsatellite stable (MSS), and the median TMB was 2.88 (0-109.44) Muts/Mb. Conclusions: Cadonilimab plus gemcitabine and cisplatin shown a promising efficacy and acceptable safety profile as first-line treatment for advanced BTC patients. Clinical trial information: NCT05978609 .

Bi-institutional spline curve analysis of lymph node mapping in gallbladder cancer operated over 12 years: Impact of location and number of lymph nodal stations.

e16274 Background: Current staging system for gallbladder cancers (GBC) takes into account only the number of metastatic lymph nodes without addressing their location. The current study evaluates the prognostic impact of lymph node mapping (number and location) in node positive GBCs. Methods: Prospectively maintained operative database of GBC patients with positive lymph nodes were analysed from two tertiary cancer care centers in a retrospective cohort study design between April 2010 till March 2022. Nodal burden was assessed including both, the number of metastatic nodes and the lymph node station. Impact of lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) was evaluated using regression and spline curve analysis. Results: Amongst 1312 operated GBC patients, 272 patients with node positive disease were included. The median nodal yield was 8. The median LNR and LODDS was 0.222 and -0.48 respectively. The 5-year DFS and OS for patients with only cystic node metastases was 52.3% and 50.8% respectively (median: not reached), as compared to 24.6% and 35.2% for involvement of regional nodal stations beyond cystic nodes. Higher LODDS was associated with inferior DFS and OS when compared to the LNR. On multivariate analysis, multi-station involvement was the only factor associated with inferior DFS (p &lt; 0.001) and OS (p = 0.007). Conclusions: Station wise pathological assessment of lymph nodal involvement could potentially provide superior prognostic information, in addition to number of involved nodes. Involvement of cystic lymph node alone has relatively superior prognosis as compared to multi-station involvement.

A single institution’s experience with robotic resections of biliary tract cancers: an analysis of the short-term outcomes and long-term survival

IntroductionPerihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma (IHCC), and gall bladder cancer are difficult malignancies to treat and are characterized by a tendency for local recurrence and a generally unfavorable prognosis. Surgical resection offers the only potential cure, conventionally performed via the open approach. Although minimally invasive approaches show promise, data remain limited. MethodsWith the institutional review board’s approval, we prospectively followed 100 patients between 2013 and 2023 who underwent robotic surgical resection for perihilar, IHCC, and gallbladder cholangiocarcinoma. Data are presented as median (mean ± SD). Significance was accepted at P ≤ .05. ResultsThe median patient age was 70 years, and the median operative duration was 333 min, with an estimated blood loss of 200 mL. Importantly, no unplanned conversions occurred, and only 1 intraoperative complication occurred within the IHCC cohort. The median length of stay was 4 days. There were a total of 19 postoperative complications and 19 readmissions within 30 days. Additionally, there were 3 in-hospital mortalities and 5 90-day mortalities. R0 resection was achieved in 87% of patients and R1 resection in 13%. At a median follow-up of 36 months, 62% of patients demonstrated disease-free survival, whereas 6% continued to live with the disease, and 32% did not survive. ConclusionOur experience demonstrates the feasibility and safety of robotic resection for these complex malignancies, yielding promising short-term outcomes. Further investigation is required to ascertain the long-term oncologic outcomes.

Establishing palliative care in tribal and rural Indian setting: A participatory action research approach.

e24085 Background: We established a palliative care center in the tribal area of Santhal Pargana, India, under a tertiary care facility, as a crucial step in addressing the palliative needs of oncology patients. This study assesses the center's inaugural year, focusing on referral patterns, morphine consumption, and pain management. Methods: Data from all patients visiting the palliative care outpatient department (OPD) in 2023 were prospectively collected and analyzed. The study focused on key palliative care indicators, including morphine consumption, patient referrals, and the mean Numeric Rating Scale (NRS) pain score after initial consultation. The PAR approach was utilized to tailor services to the community's needs. Results: The center observed an increase in patient referrals, from 8 new patients in January to 19 by December. The patient demographic primarily comprised individuals with head and neck cancer (43%), followed by breast cancer (28%) and gall bladder cancer (12%), alongside other types such as cervix, sarcomas, lung, and adult hematolymphoid malignancies. Bone metastasis was present in 46 (55.4%) patients at initial presentation. Morphine consumption demonstrated a notable rise, from 840 mg in May to 2860 mg in December, totaling 9800 mg for the year. The mean NRS pain score improved significantly from 6.5 in January to 4.3 post-initial consultation. The center maintained an overall median of 3 consultations per patient, and bereavement support was provided to 13 (15.7%) patients. Conclusions: The integration of the Participatory Action Research approach, specifically the CTC-5, was instrumental in the successful initiation and expansion of palliative care services within the center. The structured training, mentorship, and organizational restructuring, facilitated by the program, were crucial in establishing a modest palliative care infrastructure. This comprehensive approach not only enhanced care delivery but also ensured the sustainability and adaptability of palliative services, effectively addressing the gap in palliative care in rural, tribal settings.

Association between somatic mutation pathways and treatment response in patients with biliary tract cancers (BTCs).

e16196 Background: Comprehensive somatic genomic profiling has become the standard of care for patients with BTCs, serving to identify targetable mutations and aiding in prognostication. While previous studies have identified individual somatic mutations such as TP53, CDKN1A, and KRAS as negative prognostic markers, little is known about their role as predictive biomarkers. This study aimed to investigate the predictive potential of somatic mutations and pathways using commercially available next-generation sequencing. Methods: We conducted a retrospective cohort study at Beth Israel Deaconess Medical Center (BIDMC) from January 2016 to January 2023, with data censoring in January 2024. Patient characteristics, including age, gender, race, stage, site of metastasis, performance status, and survival status, were collected. Somatic genomic alterations data were extracted from FoundationOneCDx, a commercially available NGS platform designed to capture 324 genetic alterations validated for therapy targets or unambiguous drivers of oncogenesis. Genetic alterations were classified into 14 oncogenic pathways constructed based on the TCGA and Reactome databases. Multivariate Cox proportional hazards regression analysis was performed between pathway alterations, progression-free survival and overall survival, accounting for selected covariates with p &lt; 0.05 or potential known confounders. Results: Among 97 BTCs, 90 were successfully sequenced. Among these, 40 patients received gemcitabine and cisplatin, and 28 received fluorouracil and oxaliplatin (FOLFOX) therapy. Intrahepatic cholangiocarcinoma was present in 70% of cases, perihilar or distal cholangiocarcinoma in 27%, and gallbladder carcinoma in 3%. At presentation, 18% had stage I disease, and 44% had stage IV. The median follow-up time was 15 months. A total of 339 genomic alterations were identified, with 8% of samples harboring FGFR fusion or mutation, 9% IDH1 mutation, 6 % HER2 amplification, 30% KRAS mutation, and 32% with TP53 mutation. The most affected pathways were the cell cycle (66%) and DNA repair (50%). In multivariate regression analysis accounting for age, ECOG, and anatomical location, TP53 mutation was associated with shorter progression-free survival on gemcitabine and cisplatin treatment (n = 11, 2 vs. 6 months, HR 4.19, 95% CI 1.51 – 11.7, p &lt; 0.01), whereas cell cycle pathway mutation was associated with longer progression-free survival (n = 14, 6 vs. 5 months, HR = 0.43, 95% CI 0.19-0.96, p &lt; 0.05). No association was found between oncogenic pathways and treatment response to FOLFOX therapy. Conclusions: TP53 mutation is associated with a worse response, whereas cell cycle pathway mutations are associated with an improved response to gemcitabine and cisplatin therapy in patients with BTCs. Further research is needed to understand the mechanisms contributing to these observed effects.

Survival of primary gallbladder cancer in the United States: SEER database analysis from 2000-2020.

e16210 Background: Primary gallbladder cancer is a rare but aggressive cancer with poor outcomes. Our study aims to understand the survival trends of patients with Primary gallbladder cancer (PGC) and analyze the prognosis factors based on cases registered in the SEER database from 2000 to 2020. Methods: We usedSEER*Stat Version 8.4.3 software to extract primary gallbladder carcinoma cases from SEER 17 registries (2000-2020). 20,143 patients were included in the study. Those with unconfirmed histology were excluded. We analyzed overall mortality and primary gallbladder cancer-specific mortality (CSM) using a Cox proportional hazards model. The survival analysis was carried out using the Kaplan–Meier method and the log-rank test was used to compare survival curves. Results: There was an overall increase in gallbladder cancer cases by 23% in 2010-2020 compared to 2000-2010. There was no significant cancer-specific mortality difference identified between males and females (HR = 1.009; CI: 0.972-1.046). Non-Hispanic blacks had higher overall mortality (HR = 1.134; CI: 1.010-1.273) amongst different ethnicities. Crude analysis revealed overall mortality was higher among patients aged above 80 years (HR = 9.857; CI: 6.257-15.528). Crude analysis also revealed significantly higher cancer-specific mortality for cholangiocarcinoma (HR = 1.622; CI:1.509-1.744) amongst histological subtypes. Gallbladder cancer-specific mortality was high with regional disease (HR = 3.115; CI: 2.839-3.419) and increased significantly with distant metastases (HR = 7.169; CI 6.512-7.891). Treatment with surgery, chemotherapy, or radiation alone or in combination improved survival among patients. Conclusions: There is a significant increase in gallbladder carcinoma mortality even among patients with regional disease, and it was worse with metastatic disease. With limited early-stage diagnoses and poor overall survival rates, we recommend further research to develop effective screening methods, understand risk factors, and explore effective preventive and therapeutic strategies for primary gallbladder cancer.

Adjuvant S-1 vs. observation for resected biliary tract cancer: 5-year follow-up of the JCOG1202/ASCOT.

4119 Background: S-1, an oral fluoropyrimidine derivative, demonstrated significant improvement in overall survival (OS) over observation in patients with curatively resected biliary tract cancer (BTC) (hazard ratio [HR] 0.694, p=0.008; the 3-year OS, 67.6% vs. 77.1%, Lancet 2023). We present updated efficacy data based on a 5-year follow-up of JCOG1202/ASCOT. Methods: Patients aged 20-80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone R0/R1 resection were randomly assigned (1:1) to undergo observation or to receive S-1 (at the dose of 40 mg/m2 twice daily for 4 weeks, followed by 2 weeks of rest, for 4 cycles). The primary endpoint was OS, and the secondary endpoints were relapse-free survival (RFS), adverse events, and proportion of treatment completion. Results: From September 2013 to June 2018, a total of 440 patients (observation, n=222; adjuvant S-1, n=218) were enrolled. The final data cutoff date was June 23, 2023, and the median follow-up duration was 61.5 months. Of all the randomized patients, 215 (48.4%) had died (118 [53.2%] in the observation group; 97 [44.5%] in the S-1 group). The 5-year OS was 52.2% in the observation group and 64.1% in the S-1 group (stratified HR 0.723, 95% confidence interval [CI], 0.551-0.948; one-sided p=0.019). Of the 440 patients, 239 (54.3%) had RFS event (127 [57.2%] in the observation group; 112 [51.4%] in the S-1 group). The 5-year RFS was 45.9% in the observation group and 53.6% in the S-1 group (unstratified HR 0.797, 95% CI 0.618-1.028, stratified HR 0.761, 95% CI 0.589-0.984 in the sensitivity analysis). Most prespecified subgroup analyses (age, primary site, stage, lymph node metastases, types of resections, and serum CA19-9 levels) revealed favorable OS and RFS for the S-1 group. Conclusions: Adjuvant S-1 therapy maintained its survival benefit in a 5-year long-term follow-up, with clinically meaningful improvement in RFS, suggesting that it could be a standard of care for BTC. Clinical trial information: UMIN000011688.

Safety of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) in patients (pts) with biliary tract cancer with peritoneal metastases.

TPS4186 Background: Biliary tract cancers are rare with the majority of pts diagnosed with metastatic disease at initial presentation. Up to 20% of pts will have peritoneal metastases, resulting in symptoms of ascites, abdominal pain, and potential bowel obstruction. Despite advances in standard of care systemic treatments such as combination gemcitabine, cisplatin, and durvalumab (gem/cis/durva), penetration to peritoneal metastases may be poor. While addition of nab-paclitaxel to gem/cis increased objective response in a phase 2 study (1), SWOG 1815 did not demonstrate a significant improvement in survival with the triplet combination compared to gem/cis (2), possibly due to added toxicity. PIPAC directly delivers treatment to the peritoneal space, which could potentially reduce toxicity and improve efficacy. We aim to investigate the safety of PIPAC nab-paclitaxel plus systemic gem/cis/durva in biliary tract cancer pts with peritoneal metastases. Methods: This is an investigator-initiated, non-randomized phase 1 trial enrolling up to 12 evaluable pts using a modified phase 1 queue 3+3 design. Eligible pts must have treatment-naïve histologically or cytologically confirmed intra/extra-hepatic cholangiocarcinoma or gallbladder cancer with documented metastatic disease and visible peritoneal disease on imaging or laparoscopy. Gem/cis (800/25 mg/m2) will be administered on Days 1 and 8 of 3-week cycles; durva (1500 mg) will be administered on Day 1. Pts will receive PIPAC nab-paclitaxel (90 mg/m2) on Day 3 of Cycles 1, 3, and 5. If dose-limiting toxicities (DLTs) occur, nab-paclitaxel may be reduced to 70 mg/m2; the DLT window for each pt is 42 days after the first PIPAC. After eight 3-week cycles, durva (1500 mg) will be continued on Day 1 of 4-week cycles until disease progression or unacceptable toxicity. The primary endpoint is treatment-related adverse events (AEs) graded by NCI Common Terminology Criteria for Adverse Events version (v) 5.0. AEs will be monitored during treatment and for 4 weeks after the last dose of treatment with any agent. Secondary endpoints include objective response per Response Evaluation Criteria in Solid Tumors v1.1, peritoneal regression grading score at each PIPAC, peritoneal carcinomatosis index at time of laparoscopy, post-operative surgical complications, progression-free/overall survival, PIPAC technical failure rate, EQ-5D-5L and MD Anderson Symptom Inventory responses before/during treatment, and number of daily steps taken before/during treatment. Exploratory endpoints include characterization of sub-clonal tumor evolution/tumor microenvironment changes and PIPAC nab-paclitaxel pharmacokinetics/pharmacodynamics. Enrollment began 6/2023 and is ongoing. 1. Shroff et al, JAMA Oncol 2019. 2. Shroff et al, JCO 2023 LBA490. Clinical trial information: NCT05285358 .

282P Nivolumab and ipilimumab combination treatment in advanced intrahepatic cholangiocarcinoma and gallbladder cancer

282P Nivolumab and ipilimumab combination treatment in advanced intrahepatic cholangiocarcinoma and gallbladder cancer

End-of-life care preferences in patients with gallbladder cancer: Shifting patterns and disparities over two decades.

End-of-life care preferences in patients with gallbladder cancer: Shifting patterns and disparities over two decades.

Zanidatamab in previously-treated HER2-positive (HER2+) biliary tract cancer (BTC): Overall survival (OS) and longer follow-up from the phase 2b HERIZON-BTC-01 study.

4091 Background: For patients with BTC that has progressed after first-line therapy, prognosis is poor with a median OS of 6-9 months with subsequent chemotherapy. Zanidatamab is a HER2-targeted bispecific antibody that binds to two non-overlapping HER2 domains and crosslinks neighboring HER2 proteins. In the primary analysis of the phase 2b HERIZON-BTC-01 trial, after a median follow-up of 12.4 months (data cutoff: October 10, 2022), zanidatamab showed encouraging antitumor activity (41% confirmed objective response rate [cORR]) with rapid and durable responses and a manageable safety profile in patients with previously treated HER2+ BTC. OS data were immature at that time. Here, we report updated analyses, including OS. Methods: HERIZON-BTC-01 (NCT04466891) is an ongoing phase 2b trial assessing zanidatamab (20 mg/kg IV Q2W) in patients with HER2/ERBB2 gene amplification and immunohistochemistry (IHC) 2+ or 3+ (Cohort 1; HER2+); or 0 or 1+ (Cohort 2) locally advanced, unresectable, or metastatic BTC (gallbladder cancer, intra/extrahepatic cholangiocarcinoma) who received prior gemcitabine-containing treatment. The primary endpoint was cORR. Select secondary endpoints included duration of response (DoR), OS, and frequency and severity of adverse events (AEs). Updated efficacy analyses include only Cohort 1; safety analyses include Cohorts 1 and 2. Results: As of the data cutoff (July 28, 2023), median (range) follow-up was 21.9 (16-34) months. In the 80 patients in Cohort 1 (HER2+), treatment was ongoing for 9 (11%) patients and 20 (25%) patients remained on the study. cORR was unchanged from the primary analysis (n = 33; 41%) with 1 additional complete response (n = 2; 2.5%). The median DoR (95% CI) increased approximately 2 months to 14.9 (7.4, not reached) months. Median OS (95% CI) was 15.5 (10.4, 18.5) months; 12-month OS (95% CI) was 56.2% (44.3, 66.5). Among all 87 patients (Cohort 1 and Cohort 2), 18 (21%) experienced grade ≥3 treatment-related AEs (TRAEs). The most common grade 3 TRAEs (occurring in &gt; 2 patients) were diarrhea (4 [5%]); anemia (3 [3%]), and ejection fraction decreased (3 [3%]). Only one patient had a grade 4 TRAE (aspartate aminotransferase increased). There were no deaths due to TRAEs. Serious AEs occurred in 8 (9%) patients; 2 (2%) patients discontinued treatment due to an AE (pneumonitis and ejection fraction decreased; 1 patient each). Conclusions: With close to 2 years of median follow-up, zanidatamab demonstrated a median OS of 15.5 months and a median duration of response of 14.9 months (an increase compared with the initial report) in previously-treated patients with HER2+ BTC; a patient population with significant unmet need. With additional follow-up, safety remained manageable. A phase 3 trial of zanidatamab in the first-line setting for patients with metastatic BTC is planned. Clinical trial information: NCT04466891 .

Adjuvant tislelizumab combined with capecitabine for patients with biliary tract cancer with high risk of postoperative relapse (ACTIVE): Primary analysis from a prospective cohort study.

e16248 Background: Only 20% of biliary tract cancer (BTC) patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. This rate is even lower in patients with high-risk features. Capecitabine as an adjuvant therapy in biliary tract cancer has been verified to improve overall survival, however, the efficacy still remains limited. PD-1/L1 antibody combined with chemotherapy have been demonstrated to improve survival in advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of adjuvant tislelizumab and capecitabine following surgery for biliary tract cancer with high risk of recurrence. Methods: This was a single-center, prospective cohort phase II study. BTC patients (pts) underwent R0/R1 resection with high postoperative recurrence risk were eligible. The high-risk factors included positive resection margins, positive lymph nodes, positive perineural invasion, and tumor &gt; 5cm in diameter. The patients were divided into two groups, the tislelizumab (TIS 200 mg Q3W for 1 year )+capecitabine (CAP D1-14, 1500mg/m2 for eight 3-weekly cycles) group and the capecitabine group. The primary endpoint was DFS (disease free survival). The second endpoints was OS (overall survival) and adverse event (AE). Results: A total of 37 pts were enrolled into the study, while 22 pts in the TIS+CAP group and 15 in CAP group, 23 males and 14 females with a median age of 66 years. According to the location of the tumor, 37.8% pts were intrahepatic cholangiocarcinoma, 21.6% were gallbladder cancer, 5.4% were distal cholangiocarcinoma and 35.1% were hilar cholangiocarcinoma. The median DFS was 16.2 months (95% CI, 8.1-26.2) in the TIS+CAP group, which was longer than CAP group (11.4 months, 95% CI 4.2-27.1). 12-month RFS rates were 56.5% and 36.6% , respectively. The most common adverse events (AEs, any grade) were rash (18.2%), vomiting (13.6%), neutropenia (13.6%) and anorexia (13.6%) in the TIS+CAP group. Conclusions: Tislelizumab in combination with capecitabine were effective and safe as adjuvant therapy, which can prolong the DFS of BTC patients with high recurrence risk after resection. Clinical trial information: NCT04782804 .

Impact of adjuvant chemotherapy on outcomes after curative-intent surgery for biliary tract cancer: A 10-year retrospective single-center study.

e16273 Background: Surgical resection remains the mainstay of treatment for biliary tract cancers (BTCs). Although adjuvant capecitabine has been shown to reduce recurrence, the best adjuvant chemotherapy remains unclear and numerous practice differences exist. Methods: This study is a retrospective review of patients with BTCs who received curative-intent resection at one institution (Montefiore Medical Center) between 01/2014 and 04/2023. The primary outcome was relapse risk. Kaplan-Meier curves and Cox regression were used to analyze relapse-free and overall survival rates. Results: 146 patients met entry criteria. Median age was 72.2 years (IQR 62.4-77.9 months) and median follow-up time was 20 months (IQR 1-111 months). 35.6% of patients had gallbladder cancer and 64.4% cholangiocarcinoma. 57 patients (39%) relapsed and 30 patients (20.5%) died. 105 patients (71.9%) received adjuvant chemotherapy (41% single agent, 42.9% a double-agent regimen, and 16.2% triple-agent therapy). Examining individual factors (univariate analysis) revealed several linked to higher relapse risk. Patients with advanced cancer stages (III-IV vs I-II) had 2.1 times higher risk. Higher T stages also showed increased risk: 5.6 times greater for T2 and 6.7 times greater for T3 compared to T1. Additionally, positive lymph nodes (N+), elevated post-surgical CA19-9, and presence of lymphovascular or perineural invasion were all significantly associated with 1.88-2.78 times higher relapse risk. Surprisingly, receipt of adjuvant chemotherapy was associated with a higher relapse risk (HR 2.42, 95% CI 1.18, 4.95, p-value 0.015). The association between receipt of adjuvant chemotherapy and relapse remained significant (HR 2.41, 95% CI 1.09-5.35, p = 0.03), after adjusting for age, sex, residual CA19-9, and receipt of adjuvant radiation therapy. Higher overall stage (III-IV vs I-II) was identified as a significant predictor of poorer overall survival (OS) with a hazard ratio of 21.70 (2.94-27.70, p = 0.009). Node-positive disease (HR = 2.25, 1.05-4.80, p = 0.036) and relapse (HR = 3.61, 1.58-8.28, p = 0.002) were also independently associated with worse OS. Conclusions: Adjuvant chemotherapy is commonly given after curative-intent surgery for BTCs at our center. Numerous factors are associated with an increased risk of relapse. Receipt of adjuvant chemotherapy was associated with a higher relapse risk even after adjustment for multiple covariates; the reason for this association remains unclear. More studies are needed to better understand the role and best form of adjuvant chemotherapy in the treatment of BTCs.

In vitro cell killing proficiency of autologous immune cells educated with allogenic multi-cancer tumor cell lysate.

e14675 Background: Allogenic tumor lysate therapies offer a novel approach in oncology, to initiate a measured immune system response to combat cancer. Loaded with tumor antigens, these lysates stimulate the patient's immune system for targeted cancer cell destruction. In vitro data suggesting efficacy is pivotal prior to clinical trials. Per-C-Vax is a novel, organ-agnostic, allogenic tumor lysate immuno-stimulant, and is intended to target solid organ malignancies via subcutaneous injection. It is derived from a multi-organ cell-line cocktail, which has been induced into apoptosis to capture diverse Tumor Associated Molecular Patterns (TAMPs) and Damage Associated Molecular Patterns (DAMPs). Our study assesses Per-C-Vax-educated patient-specific immunocytes' in-vitro cell-killing activity against their autologous tumor cells. Methods: We collected simultaneous blood and tumor tissue samples from 22 patients with solid organ tumors under approved protocols. The cohort included 10 head and neck (45%), 4 breast (18%), and 8 other cancers (36%) comprising colorectal, ovary, lung, gallbladder, prostate, uterine, cervix, and gastric cancers. Peripheral Blood Mononuclear Cells (PBMCs) from a 10 ml venous draw were split into control and Per-C-Vax incubated aliquots for each patient. Approximately 1,000 tumor cells, stained with Calcein AM, were co-cultured with about 20,000 cells from each of the Per-C-Vax and control PBMC aliquots (autologous). Imaging-based pre- and post-co-culture counts determined the cell-kill rate for each aliquot. Results: PBMCs not treated with Per C Vax showed a significantly reduced cancer cell killing activity against autologous tumor cells compared to Per-C-Vax -treated PBMCs, suggesting the tolerogenic characteristic of immunocytes to the malignancy (0%-32%, 95% CI 10.16 to 16.65). On the other hand, PBMCs treated with Per-C-Vax showed significant cell-kill activity ranging from 46% to 84% in head and neck (mean 62.1%, 95% CI 52.67 to 71.53), 51% to 73% in breast (mean 62%, 95% CI 44.33 to 79.67), 38% to 87% in other cancers (colorectal, ovary, lung, gallbladder, prostate, uterine, cervix, gastric) (mean 50.87%, 95% CI 37.71 to 64.04). A comparative analysis between the untreated group and the group treated with Per-C-Vax revealed a statistically significant result with a p-value &lt;0.005. Conclusions: Patient-specific PBMCs incubated with Per-C-Vax tumor lysate immuno-stimulant show significant autologous cancer cell killing activity against multiple cancers in vitro. Human trials to establish safety and efficacy are planned.

THU-187 Landscape of gall bladder cancers in India: a 25 years experience at a tertiary care cancer centre

THU-187 Landscape of gall bladder cancers in India: a 25 years experience at a tertiary care cancer centre

Computed Tomography Evaluation of Gall Bladder Mass with Histopathological Correlation

Background: In extrahepatic biliary carcinoma patients, unresectable disease is frequently discovered during exploration despite thorough preoperative assessment, leading to unnecessary laparotomy. Gallbladder carcinoma ranks fifth among gastrointestinal malignancies, following colorectal, pancreatic, gastric, and esophageal carcinomas. Aim of the study: The aim of the study was to establish the diagnostic usefulness of computed tomography (CT) in the diagnosis of gallbladder mass. Methods: This case-control study was conducted at the Department of Radiology and Imaging, Rajshahi Medical College Hospital, Rajshahi, Bangladesh from March 2018 to August 2018. The study included 65 patients diagnosed with a gallbladder mass, selected through purposive sampling. SPSS version 23.0 was utilized for data analysis. Results: CT scans accurately predicted various features of gallbladder mass, showing high sensitivity, specificity, and accuracy, with positive and negative predictive values of ≥95% for adenocarcinoma, squamous carcinoma, cholecystitis, metastases, GB polyp, and adenoma. Chronic cholecystitis sensitivity was over 83%. Overall, CT diagnosis performed at least 88.9% across all features. The histopathological assessment also detected nearly similar features of gallbladder mass. Conclusion: Computed tomography (CT) serves as a valuable diagnostic tool for distinguishing gallbladder neoplasms preoperatively. It is worth noting that CT scans aid in the rational management approach for patients with gallbladder neoplasms.

Tislelizumab in combination with GEMOX and lenvatinib for conversion therapy of unresectable extrahepatic biliary tract carcinoma (eBTC): A prospective, single-arm, phase 2 study.

e16163 Background: Resection is the only possibility for cure but only less than 1/3 patients with BTC are diagnosed at resectable stages. PD-1 monoclonal antibody plus GEMOX and Lenvatinib regimens have shown promising efficacy for intrahepatic cholangiocarcinoma. However, owing to the extrahepatic and intrahepatic BTC are highly heterogeneous, the efficacy of combination regimen on eBTC is not clear. In this study, we explored the efficacy and safety of Tislelizumab plus GEMOX and Lenvatinib for conversion therapy of unresectable eBTC. Methods: In this prospective, single-arm phase 2 study, major eligible criteria were unresectable locally advanced or metastatic extrahepatic BTC, no previous systemic treatment, ECOG PS 0 or 1. Patients received tislelizumab (200 mg, iv, d1, every 3 weeks) in combination with GEMOX (gemcitabine: 1000 mg/m2, iv, d1,d8, every 3 weeks; oxaliplatin: 85 mg/m2, iv, d1, every 3 weeks) and Lenvatinib (bodyweight ≥ 60 kg: 12 mg/day; &lt; 60 kg: 8 mg/day, po) until disease progression, intolerable toxicity or surgery. Surgery was performed after treatment response was assessed to meet the criteria of resection. Primary endpoint was the rate of radical resection. Second endpoints included ORR, DCR per RECIST 1.1, and safety, major pathologic response (MPR), PFS, OS. Results: Between Mar 1st 2022 and Feb 1st 2024, 35 patients were enrolled with a median age of 57.5 years (range 52-65); 20 males (57.1%), 15 females (42.9%); ECOG PS 0 (n = 13, 37.1%) or 1 (n = 17, 62.9%); 7 distal cholangiocarcinoma (20.0%), 16 hilar cholangiocarcinoma (45.7%), 12 gallbladder carcinoma (34.3%). 30 patients were evaluated for tumor response. The best overall responses were 2 complete response (6.7%), 16 partial response (53.3%), 9 stable disease (30.0%) and 3 progressive disease (10.0%). The ORR was 60.0% and DCR was 90.0%. 7 patients (20.0%) received radical resection and the complete pathological response (pCR) rate was 42.9% (n = 3). Any-grade adverse events (AEs) occurred in 91.4% (n = 32) patients. Grade 3-4 AEs occurred in 20.0% (n = 7) patients. The most frequent grade 3-4 AEs (incidence &gt; 5%) were thrombocytopenia (8.6%), elevated AST/ALT (8.6%), neutropenia (5.7%) and leukopenia (5.7%). No grade 5 AEs. Conclusions: Tislelizumab plus GEMOX and Lenvatinib showed promising efficacy with manageable safety profile for conversion therapy of unresectable extrahepatic BTC. More patients were recruiting to further prove these results. Clinical trial information: ChiCTR2200056808.