bluuebunny/crossref_metadata_2025 huggingface dataset:
Front-line use of FOLFOXIRI plus bevacizumab and subsequent therapies in metastatic colorectal cancer (mCRC).
Authors: Barzi Afsaneh , Lunacsek Orsolya , Pisa Federica , Pan Xiaoyun , Ostojic Helene , Vassilev Zdravko
Published: January 2024

45

Background: Emerging data shows that the higher incidence of mCRC in younger patients (pts) is accompanied by more aggressive front-line treatment with chemotherapies, such as FOLFOXIRI+bevacizumab (triplet+bev). We explored the use of triplet+bev and subsequent therapies in a representative sample of community practices in the USA. Methods: This was a retrospective study using the nationwide de-identified Flatiron Health Electronic Health Record-derived database from January 1, 2013, to February 28, 2023. The use of triplet+bev and subsequent treatments were analyzed in pts with newly diagnosed mCRC (≥18 years [yrs] of age) by oncologist-defined, rule-based line of treatment (LOT) and age (18–49, 50–64, and ≥65 yrs). Results: Of 24,285 eligible pts, 14%, 37%, and 49% were 18–49, 50–64, and ≥65 yrs at treatment initiation, respectively (Table). Triplet+bev use in any LOT was the most prevalent in the youngest age group (18–49 yrs) at 7% (Table). Two-thirds (67%) received triplet+bev in first line (1L) and 23% in second line (2L), 57% were male, and 34% had a KRAS mutation (23% missing). From 2013 to 2022, triplet+bev use in newly treated pts increased; this trend was more pronounced in pts 18–49 yrs (Table). Among pts not censored before the end of the respective LOT, median duration of 1L and 2L triplet+bev was 25.1 and 21.6 weeks, respectively (Table). For non-censored pts with and without a KRAS mutation, respectively, median duration of triplet+bev was 26.1 vs 23.5 weeks in 1L and 21.6 vs 16.5 weeks in 2L. Most frequently used new agents after 1L triplet+bev included anti-EGFR (panitumumab or cetuximab; 19%), TAS-102 (12%), regorafenib (10%), and capecitabine (3%). Most frequently used new agents after 2L triplet+bev were TAS-102 (21%), anti-EGFR (17%), regorafenib (15%), and pembrolizumab (8%). Conclusions: Our study shows that the use of triplet+bev has increased in pts with mCRC over time, particularly in those <50 yrs. Most frequent subsequent therapies across all pts following 1L and 2L triplet+bev included TAS-102, anti-EGFR, and regorafenib. Future research is needed to identify the optimal treatment strategies after triplet+bev. [Table: see text]
Treatment patterns of gemcitabine-based chemotherapy in patients with de novo and recurrent advanced biliary tract cancer.
Authors: Dayyani Farshid , Stirnadel-Farrant Heide A. , Hu Jenny , Lin Yian , Kebede Nehemiah , Valerio Stephen J. , Ahn Daniel H.
Published: January 2024

454

Background: Biliary tract cancers (BTC) are often diagnosed at advanced stages (aBTC) when prognosis is poor. In the Phase 3 TOPAZ-1 study (NCT03875235), durvalumab plus gemcitabine and cisplatin (GemCis) significantly improved overall survival versus placebo plus GemCis. To better understand the context of the TOPAZ-1 trial results in the US, we looked at first-line (1L) treatment patterns in participants with aBTC treated with GemCis and other gemcitabine (Gem)-based chemotherapy (CT) regimens. Methods: This retrospective observational cohort study used linked electronic health records and medical and pharmacy claims data from the Optum Market Clarity Database. Adults diagnosed with de novo or recurrent aBTC, who initiated 1L Gem-based CT between January 2016 and March 2022, were identified and followed from the index date (defined as the first administration of Gem-based CT on or after initial BTC diagnosis date) until death, end of continuous enrollment, or end of study period, whichever occurred first. Variables including patient demographics, clinical characteristics, and treatment patterns were described. Results: A total of 580 patients were included in the analysis with either de novo aBTC (n=481, 82.9%) or recurrent aBTC (n=99, 17.1%) with median follow-up time of 10.4 (interquartile range: 6.4, 17.5) and 12.0 (interquartile range: 6.3, 21.9) months, respectively. Mean (SD) age was 64.6 (11.2) and 66.8 (10.4) years, with 45.7% and 54.5% male in the de novo and recurrent aBTC groups, respectively. Most patients were white (77.6%). The most frequent site of primary tumor diagnosis was single-site intrahepatic (overall 62.8%, de novo 66.7%, recurrent 43.4%). In the 12 months prior to index date, 38.5% of patients had biliary obstruction, 30.2% had biliary stents, 29.3% had jaundice, and 17.1% had nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Common comorbidities included cardiovascular disease (50.9%), obesity (46.8%), and diabetes (35.2%). The most common 1L CT was GemCis followed by Gem for both the de novo (n=355, 73.8% and n=36, 7.5%) and recurrent groups (n=58, 58.6% and n=26, 26.3%), respectively. Approximately half of participants (50.9%) switched to a new line of treatment, 33.3% discontinued 1L CT, and 15.9% remained on 1L CT at last follow-up. Most frequent 2L treatments included fluorouracil/oxaliplatin (36.9%) and capecitabine (14.2%). Further analysis will characterize outcomes and regimen duration. Conclusions: Findings from this retrospective study showed that the most common 1L therapies were GemCis and Gem among both de novo and recurrent patients with aBTC. These results provide insight into aBTC treatment practices and may help inform treatment decisions.
Real-world testing, treatment patterns, and outcomes following liquid biopsy in advanced cholangiocarcinoma.
Authors: Mahipal Amit , Clemens Keelia M. , Liao Jiemin , Weipert Caroline M. , Bucheit Leslie , Khushman Moh'd M.
Published: January 2024

455

Background: Cholangiocarcinoma (CCA) is an aggressive cancer with a poor prognosis. Given failure rates of up to 27% of CCA tissue biopsies, liquid biopsy has become an important tool to identify actionable molecular alterations. It is estimated tissue-based testing identifies IDH1 mutations and FGFR2 fusions in 12% and 9% of patients with advanced CCA (aCCA), respectively. Here we examined the rate of molecular alteration detection using circulating tumor DNA (ctDNA) testing, treatment patterns in aCCA, and outcomes for patients receiving ivosidenib following ctDNA-detected IDH1 mutations. Methods: Real-world data was sourced from GuardantINFORM, which comprises aggregated commercial payer health claims and de-identified records from >330,000 patients with clinical ctDNA testing via Guardant360 (G360), from 2014 to 2023. Patients with aCCA and >1 treatment claim after G360 results were included (N=1726). Patient outcomes were assessed via real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS), all assessed in months. Log rank test was used to compare Kaplan-Meier survival curves. Results: Of 1495 patients with >1 ctDNA alteration detected, a guideline-recommended biomarker was identified in 18% of patients. In patients with intrahepatic CCA (n=403), 11% had an IDH1 mutation, 9% an FGFR2 fusion, 1% MSI-H detected, 1% BRAF V600E mutation, <1% ERBB2 amplification and <1% RET fusion. Testing was performed prior to first-line therapy, after first-line therapy and after second-line therapy in 34%, 46% and 21% of patients respectively. Gemcitabine and cisplatin represented the most common first-line therapy (48%). FOLFOX (21%), gemcitabine and cisplatin (13%), and capecitabine (11%) were the most common second-line therapies. Among ivosidenib-naïve patients with an IDH1 mutation, 58 (20%) started therapy within 90 days of ctDNA test: 36% received ivosidenib, 57% received chemotherapy, 7% received other therapy. Patients with IDH1 mutations treated with ivosidenib (n=21) had numerically improved rwTTD and rwTTNT compared to those receiving chemotherapy (n=33) [rwTTD: 4.6 (95% CI:2.6-8.6) vs 2.8 (95% CI:2.0-6.3), p=0.1011; rwTTNT 11.0 (95% CI:5.7-NE) vs 5.2 (95% CI:3.3-NE); p=0.2559]. There was no difference in rwOS between patients receiving ivosidenib vs not. However, sample size was small. Conclusions: The rate of actionable molecular alterations detected via ctDNA is 18%, comparable to reports from tissue-based testing. Patients with aCCA are often tested before starting first or second LOT. Patients with ctDNA-detected IDH1 mutations treated with ivosidenib and had a trend toward improved rwTTD and rwTTNT, although it did not reach statistical significance. This data supports the clinical utility of liquid biopsy to identify aCCA patients who may benefit from targeted therapy.
Characterization of outcomes and genomic alterations (GA) in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA).
Authors: Haro-Silerio Jaime , Fox Daniel Aaron , Bhamidipati Deepak , Hu Zishuo Ian , Koay Eugene Jon , Ludmir Ethan B. , Tran Cao Hop Sanderson , Vauthey Jean-Nicolas , Newhook Timothy E. , Tzeng Ching-Wei D. , Chun Yun Shin , Mahvash Armeen , Metwalli Zeyad , Habibollahi Peiman , Cox Veronica L. , Kang Hyunseon , Chatterjee Deyali , Kaseb Ahmed Omar , Javle Milind M. , Lee Sunyoung S.
Published: January 2024

458

Background: Hepatobiliary cancers comprise a heterogeneous spectrum of invasive carcinomas involving the liver and bile ducts. Due to its rarity, the prognosis and clinical outcomes data are poorly understood. This study aims to provide insight into the response to therapeutic options and GA in patients (pts) with cHCC-CCA. Methods: We conducted a retrospective analysis of clinical outcomes data and GA at MD Anderson (MDA) from 2009 to 2023 in pts with cHCC-CCA. Pt characteristics were compared using Fisher’s exact test and Mann-Whitney U. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and the log-rank test. Results: 40 pts with cHCC-CCA were analyzed. Hepatitis B and C were the most common etiologies (Table). 25.0% had portal vein tumor thrombus and 72.0% had advanced disease (M1/N1) at diagnosis. Radiographic washout was seen in 55.9%. Elevation of CA19-9, AFP, and both was in 42.5, 57.5, and 30.0%. Cirrhosis at diagnosis was 35.0%. Pts who underwent surgery (n=10) had significant OS benefit (55.6 vs. 14.1 m, p<0.001). Y90 (n=4)/radiation therapy (n=10) provided significant OS benefit in pts who did not undergo surgery (23.3 vs 10.9 m; p=0.012). 34 pts received 1st line systemic therapy: 10 pts received gemcitabine/cisplatin (GC) combined with immunotherapy (GCI): GC + nivolumab (n=5), durvalumab (n=3), or atezolizumab/bevacizumab (AB, n=2). GCI was compared to other regimens (OR, n=24) including chemotherapy alone (GC, FOLFIRI, FOLFOX), HCC-directed therapy alone (AB, lenvatinib, nivolumab), or chemotherapy plus lenvatinib or bevacizumab with mPFS of 7.0 vs. 2.9 m (p=0.014) showing significant PFS benefit. Pts who received GCI trended to better OS compared to OR (18.9 vs. 12.0 m, p=0.380). 2 pts treated with GC+AB had complete responses to date at 36.0 and 14.0 m. Of 31 pts who underwent GA testing, the 2 most frequent GAs were TP53 (38.7%) and TERT (35.5%) mutations. Neither impacted OS: TP53 15.8 vs. 17.6 m (p=0.746); TERT 9.8 vs. 23.3 m (p=0.355). Conclusions: GCI had survival benefit compared to OR in cHCC-CCA. Pts who present with early stage of disease should be evaluated early for surgical resection or maximize local therapy in the case of nonresectable disease to improve survival. [Table: see text]
Clinical characteristics and the course of hepatobiliary and pancreatic malignant tumors with high microsatellite instability after pembrolizumab administration: A multicenter observational study.
Authors: Maruki Yuta , Ikezawa Kenji , Sasaki Mitsuhito , Kobayashi Satoshi , Todaka Akiko , Tsumura Hidetaka , Okano Naohiro , Terashima Takeshi , Yamashita Tatsuya , Kawamoto Yasuyuki , Kojima Yasushi , Imaoka Hiroshi , Hosoi Hiroko , Morizane Chigusa , Ueno Makoto , Ikeda Masafumi , Okusaka Takuji
Published: January 2024

459

Background: The Keynote-158 trial have resulted in an expanded approval for pembrolizumab (Pem) in solid tumors with high microsatellite instability (MSI-H). In the trial, Pem was administered to patients with MSI-H solid tumors, excluding colorectal cancer, and the overall response rate (ORR) was 34%. However, the ORR for pancreatic (PANC) and biliary tract (BT) cancer were 19% (4/22 cases) and 41% (9/22 cases), respectively, suggesting the possibility of varying treatment efficacy by the primary tumor site. In this study, we aimed to clarify the clinical characteristics of patients with MSI-H and the efficacy of Pem administration in hepatobiliary and pancreatic (HBP) cancers. Methods: A multicenter observational study of patients with HBP cancer with MSI-H was conducted from March 2020 to March 2023. This study consists of prospective and retrospective cohorts. We evaluated the efficacy of PEM administration in patients with PANC and BT, respectively. Results: We enrolled 51 patients, including 32 in the prospective cohort; males comprised 51% of the patients. The BT, PANC, and liver were the primary sites in 26, 24, and 1 patients, respectively. MSI-H diagnostic methods were the MSI kit (FALCO) and comprehensive genome profile in 43 (84%) and 8 (16%) patients, respectively. Intrahepatic cholangiocarcinoma (ICC) was the most common cancer in BT tumor; ICC was observed 13 (50%) patients, followed by perihilar, gallbladder, and distal bile duct (including ampullary cancer) cancers in 6, 4, and 3 patients, respectively. Some rare histological types were observed, two patients had neuroendocrine carcinoma and one had hepatoid carcinoma in PANC. One had an undifferentiated carcinoma in BT. Five and six patients with PANC and BT tumors, respectively, had one or more first-degree relatives with lynch syndrome-related disease. Pem was administered to 96% and 88% of the patients with PANC and BT tumors, respectively. The ORR was 30% in PANC and 73% in BT tumors (p=0.003). In BT tumor, three patients demonstrated complete response as follows: two with ICC and one with perihilar cholangiocarcinoma. The median progression-free survival was 3.2 months (95% confidence interval [CI], 1.3–14.4) and 16.3 months (95% CI, 8.7 to not reached) in patients PANC and BT tumors (p=0.08), respectively. Grade 3/4 immune-related adverse events occurred in 13% and 29% of the patients with PANC and BT tumors, respectively. Conclusions: ICC was the most common BT cancer with MSI-H. Pem was significantly more effective in BT tumors than in PANC tumors, with higher ORR. Clinical trial information: UMIN000040591 .
Real-world (RW) testing patterns of serum lactate dehydrogenase (LDH) and its prognostic value among patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Lenz Heinz-Josef , Lunacsek Orsolya , Ostojic Helene , Pan Xiaoyun , Dochy Emmanuelle , Vassilev Zdravko , Khan Nasreen
Published: January 2024

46

Background: LDH is a potential prognostic biomarker of outcomes for pts with mCRC. This retrospective, observational cohort study describes RW LDH testing patterns and assesses LDH as a prognostic factor for overall survival (OS) in pts receiving chemotherapy (CT) for mCRC in the USA. Methods: Pts with mCRC, ≥18 years (yrs) of age, who initiated first line (1L) CT (index date) between January 1, 2016, and November 30, 2022, were identified in the nationwide de-identified Flatiron Electronic Health Record-derived database. Practice patterns for LDH testing are described. Pts were categorized into normal vs abnormal LDH baseline (≤3 months prior to/at index date) value based on the lab reference range. Prognostic relationship between normal vs abnormal LDH baseline value and OS was assessed using Kaplan-Meier and multivariate Cox proportional-hazards model. Results: Of 15,329 eligible pts, 57% were male, 49% were ≥65 yrs of age and 66% had ECOG performance status 0–1; 59% had stage IV disease at initial diagnosis; 29% had a KRAS mutation (at any time ≤30 days post-index; 35% not tested). Median time from mCRC diagnosis to index was 35 days. Most common 1L regimens were FOLFOX ± bevacizumab (48%), FOLFIRI ± bevacizumab (15%), and capecitabine (13%). Median follow up from index date was 15.6 months (mos); 60% died. LDH testing was performed in 2,547 pts (17%) during baseline and 3,379 pts (22%) post-index. Among those with ≥1 LDH test during each line of therapy (LOT), median number of LDH tests per pt was 4–6 and median time from line initiation to first LDH test was 7–10 days across the first five LOTs (Table). Among LDH tested pts during follow-up (n=3,379), 21% and 40% had abnormal and normal LDH values at baseline, respectively (39% missing). Demographic characteristics of abnormal vs normal LDH pts were similar; abnormal LDH pts were more likely to be ≥65 years (52% vs 49%), African American or Black (12% vs 7%), and reside in the Northeast (30% vs 21%). Median OS (95% CI) in pts with normal vs abnormal baseline LDH was 29.9 (28.3, 31.7) mos vs 16.8 (14.8, 18.2) mos. In multivariate Cox proportional-hazards model, pts with abnormal baseline LDH values had higher risk of death (HR 1.91, p<0.0001) after adjustment for pt demographic and clinical characteristics. Conclusions: In RW clinical practice in the USA, only one-fifth of mCRC pts receiving CT undergo LDH testing even though LDH value has been found to be a prognostic factor of OS. Efforts to increase LDH testing may help guide treatment decisions in this setting. [Table: see text]
Outcomes and prognostic factors of advanced biliary tract cancers in Saudi Arabia.
Authors: Alshammari Kanan , Alduaiji Reema , Alotaibi Lena , Alqadiri Reema , Alqahtani Laila , Alotaibi Faizah , Al-Fayea Turki , Sabatin Fouad , Alolayan Ashwaq , Alkaiyat Mohammad , Shehata Husam , Al Qahtani Joud , Algarni Mohammed Ahmed
Published: January 2024

460

Background: Biliary tract cancers which include gallbladder adenocarcinoma, intrahepatic and extrahepatic cholangiocarcinoma are rare, and carry a poor prognosis. There is limited data on biliary tract cancers in the Saudi population. Methods: This single center retrospective study was conducted with data of eligible cases from the last 4 years. Survival, chemotherapy regimens, and variables such as neutrophil to lymphocyte ratio (NLR), and other potential prognostic variables were collected. Results: The study included 155 patients of which 75 had intrahepatic cholangiocarcinoma and 74 had gallbladder adenocarcinoma. The majority were females at 63% of patients. Overweight to obese patients represented 59% of the study cohort. The majority of patients (62%) had an ECOG performance status of 2 and below. Comprehensive genomic profiling was done to 20% of cholangiocarcinoma cases. Elevated CA19-9 tumor marker (> 37 micromol/L) was found in 57% of patients. De novo metastatic disease affected 82% of patients. One third of patients (33%) were not fit for first line chemotherapy, and were given best supportive care. First line chemotherapy of platinum + gemcitabine was given to 53% of fit patients, followed by gemcitabine alone given to 38%, followed by 5-Fluorouracil chemotherapy given to 9% of patients. Very few patients lived for 12 months or more at 16%. There was a significant association between NLR and progression free survival (PFS) with median PFS being 3.5 months in the NLR > 3 group (95% CI 1.2-6 months) versus median PFS of 9.8 months in the NLR < 3 group (95% CI 7.5-12 months, p=0.019). Conclusions: Biliary tract cancers still carry a poor prognosis. NLR ratio of more than 3 was found to predict a low PFS.
Single-institutional analysis of radiotherapy and orthotopic liver transplant for patients with unresectable cholangiocarcinoma.
Authors: Hsieh Meng-Lun , Hannan Sumehra , Hanish Steven I. , Vagefi Parsia A. , Singal Amit G. , Wang Andrew Zhuang , Shah Jigesh A. , Mufti Arjmand R. , Sanford Nina Niu , Patel Madhukar S. , Rich Nicole E. , Aguilera Todd Anthony
Published: January 2024

466

Background: There is increasing interest in effective strategies for locoregional therapy for cholangiocarcinoma, particularly given the evolving role of orthotopic liver transplant (OLT) for select patients. This single-institution retrospective study compares the clinical efficacy and toxicity of stereotactic body radiotherapy (SBRT), conventional fractionation chemoradiation (CRT), or SBRT as a bridge to OLT in patients with unresectable early stage and locally advanced cholangiocarcinoma. Methods: We reviewed a total of 31 patients from 2010 to 2023 with intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and perihilar cholangiocarcinoma who were treated with SBRT (n=22) or CRT (n=9). SBRT was delivered in 1-5 fractions, median dose of 40 Gy, and dose ranging from 16 Gy to 60 Gy. CRT was delivered in 13-28 fractions, median dose of 50.2 Gy, and dose ranging from 45 Gy to 52.5 Gy. Kaplan-Meier was used to analyze overall survival (OS), progression-free survival (PFS), and local control (LC). Acute and late G3+ toxicity was scored using CTCAE, version 5.0. Results: We identified 13 patients with ICC, 5 with ECC, and 13 with perihilar disease where SBRT or CRT was part of upfront definitive treatment. With a median follow-up time of 11 months, there was no statistical difference between SBRT vs. CRT for OS (median 21 vs. 22 months; p=0.36), PFS (median 14.2 vs. 11 months; p=0.09), and 1-year LC (73.2% vs. 66.7%; p=0.10). However, SBRT appeared to have lower proportions of acute grade 3+ (9.1% vs. 33.3%) and chronic grade 3+ toxicities (22.7% vs. 33.3%). Four patients with early stage perihilar or ICC underwent SBRT as successful bridge to transplant, with no evidence of disease progression at 5.4 months. An additional 2 out of 8 patients were removed from protocol due to disease progression and 2 others remain on protocol, awaiting OLT. Conclusions: In our series of unresectable cholangiocarcinoma, we found no difference in OS, PFS, and LC for patients treated with SBRT vs. CRT, although the former appeared to have lower toxicity and a trend towards improved PFS. Further research is needed to compare SBRT and CRT as definitive treatment or bridge to OLT for patients with unresectable cholangiocarcinoma.
Promising first-line immuno-combination therapies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.
Authors: Wen Feng , Huang Peng , Wu Qiuji , Yang Yang , Li Qiu
Published: January 2024

469

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death all over the world, bringing a heavy social economic burden especially in China. Several immuno-combination therapies have shown promising efficacy in the first-line treatment of unresectable HCC and are widely used in clinical practice. However, which combination is the most affordable is unknown. The current study assessed the cost-effectiveness of the immuno-combinations as first-line treatment for patients with unresectable HCC from the Chinese payers' perspective. Methods: A Markov model was built based on five global, multicenter, open-label, phase III randomized trials (Himalaya, IMbrave150, ORIENT-32, CARES-310, LEAP-002) to investigate the cost-effectiveness of tremelimumab plus durvalumab (STRIDE), atezolizumab plus bevacizumab (A+B), sintilimab plus bevacizumab biosimilar (IBI305) (S+B), camrelizumab plus rivoceranib (C+R) and pembrolizumab plus lenvatinib (P+L). Three disease states were included: progression free survival (PFS), progressive disease (PD), and death. Medical costs were searched from the Red Book, published literatures, and West China Hospital. Cost-effectiveness ratios (CERs) and incremental cost-effectiveness ratios (ICERs) were evaluated to compare costs among different combinations. Sensitivity analyses were performed to assess the robust of the model. Results: The total cost and quality-adjusted life years (QALYs) of C+R, S+B, P+L, A+B and STRIDE were $12,109.27 and 0.91, $26,961.60 and 1.12, $55,382.53 and 0.83, $70,985.06 and 0.90, $84,589.01 and 0.73 respectively, resulting in the most cost-effective strategy of C+R with CER of $13,306.89 per QALY followed by S+B with CER of $24,072.86 per QALY. The S+B strategy would become the most cost-effective when the willing-to-pay threshold exceeded $73,500/QALY. In the subgroup analysis, with the application of Asia results in Leap-002 trial, the model results were the same as global data. In the sensitivity analysis, with the variation of parameters, the results were robust. Conclusions: As one of the promising immuno-combination therapies in the first-line systemic treatment for unresectable HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost-effective strategy, which warranted further studies to best inform the real-world clinical practices.
Real world (RW) use and outcomes of regorafenib (REG) flexible dosing in patients (pts) with metastatic colorectal cancer (mCRC) in Europe.
Authors: Peeters Marc , Chibaudel Benoist , Barzi Afsaneh , Ostojic Helene , Pan Xiaoyun , Yasuda Marie , Chen Chi-Chang , Multani Jasjit , Casey Vicky , Vassilev Zdravko
Published: January 2024

47

Background: In the phase 2 ReDOS study, REG first-cycle dose-escalation showed comparable activity and lower incidence of adverse events in pts with mCRC vs standard dosing. This retrospective cohort analysis aimed to examine RW dosing patterns of REG and associated duration of treatment (DoT) in pts with mCRC in Europe. Methods: Data from pts with mCRC, aged ≥18 years who initiated REG monotherapy from January 1, 2019 to April 30, 2022, were collected retrospectively from chart review by physicians recruited from the IQVIA OneKey database. Pts were categorized by dosing regimen to either flexible dosing regimens (ReDOS-like [<160 mg starting dose] or dose-adjusted [160 mg starting dose with dose adjustments during treatment]) or a standard dosing regimen (160 mg throughout treatment). Results: Overall, 355 pts (France, n=146; Italy, n=143; Belgium, n=66; 68% male, 54% aged ≥65 years) were eligible for inclusion. Nearly half (49%) received a ReDOS-like regimen, 32% received a standard dosing regimen, and 19% received a dose-adjusted regimen (Table). A higher proportion of pts on a dose-adjusted regimen had ≥3 metastatic sites (64% vs 43% for standard dosing) and most had initiated ≥3 REG cycles (93% vs 67% and 64% for ReDOS-like and standard dosing regimens, respectively). Pts receiving a ReDOS-like dosing regimen had worse performance status (ECOG PS ≥2, 35% vs 30% for dose-adjusted and standard dosing) and a higher proportion of KRAS (42% vs 37% and 30% for dose-adjusted and standard dosing regimens, respectively) or NRAS (28% vs 24% and 21% for dose-adjusted and standard dosing regimens, respectively) mutations. Median DoT was longer for ReDOS-like and dose-adjusted regimens vs standard dosing (1.4 and 1.9 vs 1.0 months, respectively; Table). Conclusions: Pts receiving REG flexible dosing regimens (ReDOS-like, dose-adjusted) had longer DoT compared with a standard dosing regimen despite having a higher frequency of adverse prognostic factors. Thus, this study affirms that flexible dosing strategies are viable options for optimizing REG treatment and outcomes in pts with mCRC. [Table: see text]
Continuation rather than early induction in S-1 adjuvant chemotherapy and prognosis in patients after biliary tract cancer resection.
Authors: Hayashida Kotaro , Adachi Tomohiko , Imamura Hajime , Yamashita Manpei , Tetsuo Hanako , Matsushima Hajime , Hara Takanobu , Soyama Akihiko , Kanetaka Kengo , Eguchi Susumu
Published: January 2024

474

Background: The efficacy of S-1 monotherapy as adjuvant chemotherapy (AC) for pancreatic cancer has been demonstrated, and the long-term results are clearly improving.1 In biliary tract cancer, the JCOG1201 trial in Japan also demonstrated the usefulness of S-1 AC recently.2 We have been also performed S-1 AC for biliary tract cancer in recent years in accordance with the clinical necessity. In this article, we herein retrospectively analyze the S-1 AC for biliary tract cancer especially in the significance of initiation day or therapy continuation. Methods: 134 patients with the resection of biliary tract cancer (intrahepatic cholangiocarcinoma 25/ hilar 17/ gallbladder 27/ distal bile duct 38/ papillary 25 from January 2017 to December 2021 were included in this study. Age 73(30-87) years, 47 hepatic resections/66 pancreatecticoduodenectomies/21 peri-gallbladder resection. The decision to administer AC was made at the discretion of the attending doctor and in consultation with the patient, and the decision to discontinue was based on the patient's physical condition. If there was no particular need to discontinue, the treatment was continued for six months at least. Results: S-1 AC was performed in 57/137 (43%) of eligible patients. Age was similar between with or without AC patients (73 vs. 73 years old). There were no significant differences by the cancer location. Although pathological stage was higher in the patients with AC (stage 0:1:2:3:4 = 0: 20: 39: 31: 9%) than without AC ( = 9: 45: 33: 10: 3%) (p < 0.001), 2 years recurrence free survival (2y- RFS) was similar between with AC or without AC patients (66.6 vs 71.6%, p=0.82). In the subgroup analysis of the patients with AC, although comparisons of induction day of AC within or after postoperative 6 weeks showed no difference in patient’s prognosis, patients with continuation of AC for at least 6 months after initiation clearly had a better prognosis than without it (2y-RFS: 89.6 vs 41.7%, p=0.003). Conclusions: In S-1 AC for the patients after biliary tract cancer resection, early induction does not play much role, but continuation is important to maintain better prognosis. 1. Uesaka et al. Lancet, 2016. 2. Nakachi et al. Lancet, 2023.
A single-arm, multi-center phase II study of tislelizumab combined with lenvatinib and GEMOX as conversion therapy in potentially resectable locally advanced biliary tract cancer (ZSAB-TransGOLP): A primary analysis.
Authors: Fan Jia , Zhou Jian , Shi Guoming , Huang Xiaoyong , Gao Qiang , Li Xiaowu , Ji Yuan , Liang Fei , Chen Yi , Lu Pinxiang , Qiu Shuangjian , Ren Ning , Shen Yinghao , Xu Yongfeng , Ding Zhenbin , Zhu Xiaodong , Sun Huichuan , Shi Yinghong , Wang Xiaoying , Yi Yong
Published: January 2024

488

Background: We have previously reported that GEMOX combined with lenvatinib and PD-1 antibody (GOLP regimen) showed promising efficacy as first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA), indicating that GOLP regimen may be an ideal conversion therapy for patients (pts) with potentially resectable advanced biliary tract cancer (BTC). This phase II trial explored the efficacy and safety of GOLP as conversion therapy in potentially resectable and locally advanced BTC. Methods: Patients with potentially resectable locally advanced BTC were enrolled and received tislelizumab (200mg, Q3W) and lenvatinib (8mg, QD) and GEMOX chemotherapy (Q3W) including gemcitabine 1000mg/m2 on day 1, 8 and oxaliplatin 85mg/m2 on day 1. Tumor responses were evaluated every 9 weeks according to RECIST v1.1, and the resectability was simultaneously discussed by MDT. For pts who were eligible for surgery, capecitabine alone was administered as adjuvant therapy after radical surgery. Pts who was not suitable for surgery continued to the original treatment regimen until progression or intolerable toxicity. The primary endpoint was R0 resection rate, and secondary endpoints included ORR, DCR, PFS, OS, CPR, MPR, RFS. Results: From December 2021 to July 2023, 41 pts were enrolled, 21 males and 20 females with a mean age of 57 years. 87.8% pts had iCCA, 7.3% had perihilar bile duct cancer and 4.9% had gallbladder cancer. TNM stage was II, IIIA, IIIB and IIIC for 2.4%, 34.1%, 58.5% and 4.9% of pts respectively. At cut-off date (September 10, 2023), the mean follow-up was 7.7 months, 39 pts completed at least three cycles of conversion therapy and 7 pts still administered with scheduled conversion therapy. The ORR was 43.9% (18/41) and the DCR was 87.8% (36/41). The median duration of therapy before surgery was 2.9 months (95%CI 2.6-4.6), R0 resection rate was 48.8% (20/41), and 2 pts underwent R1 resection. 9.1% (2/22) pts had a pCR and 22.7% (5/22) had an MPR. The most common grade 3/4 treatment-related adverse events (TRAEs) included neutropenia (31.7%), increased GGT (19.5%), leukopenia (12.2%). No grade 5 AEs occurred. Conclusions: This study demonstrates the high effectiveness and manageable safety of GOLP regimen as conversion therapy for potentially resectable locally advanced BTC. Survival data will continue to be followed up. Clinical trial information: NCT05156788 .
Comparison of the treatment effect between lenvatinib and atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in pathologically diagnosed metabolic dysfunction–associated steatotic liver disease.
Authors: Takahashi Hirokazu , Koshiyama Yuichi , Mitsumoto Yasuhide , Kobayashi Takashi , Hayashi Hideki , Arai Taeang , Sawada Koji , Nonaka Michihiro , Nakahara Takashi , Tomita Kengo , Ito Takanori , Notsumata Kazuo , Seko Yuya , Fujii Hideki , Aishima Shinichi , Yoneda Masato , Toyoda Hidenori , Sumida Yoshio , Nakajima Atsushi , Okanoue Takeshi
Published: January 2024

493

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading etiologies of HCC. Recent evidence indicates that MASLD might affect the response to immune checkpoint inhibitors and multi-receptor tyrosine kinase inhibitors in the treatment for unresectable hepatocellular carcinoma (HCC), yet real-world data with accurate pathological diagnosis of MASLD has not been confirmed. Methods: Patients with unresectable HCC who had been pathologically diagnosed with MASLD by liver biopsy and/or hepatectomy and later received treatment with lenvatinib (LEN) or atezolizumab plus bevacizumab (ATZ/Bev) as first-line systemic treatment for HCC were included. Outcomes of treatment with LEN or ATZ/Bev were compared. Results: A total of 48 patients who received LEN (n=26) and ATZ/Bev (n=22) were included. The mean time from pathological diagnosis to the initiation of treatment was not different (LEN 1,542 days, ATZ/Bev 1,260 days; p=0.48). The degree of steatosis, inflammation, ballooning hepatocytes and fibrosis did not differ between LEN and ATZ/Bev. At the initiation of treatment, BCLC stage, albumin–bilirubin grade, and Child–Pugh grade did not differ between LEN and ATZ/Bev. The overall response rate and disease control rate evaluated with modified RECIST criteria were not different between LEN and ATZ/Bev (26.1% and 77.2% for LEN, and 22.7% and 70.8% for ATZ/Bev). Median progression-free survival (PFS) was not different between LEN and ATZ/Bev (266 days vs 287 days, p=0.278). Median overall survival (OS) of LEN tended to be longer than that of ATZ/Bev (1364 days vs 663 days, p=0.081). The potential advantage of LEN in OS was statistically significant in the patients with Child-Pugh score = 5 (P=0.0443). A total of 17 patients received both LEN and ATZ/Bev treatment and order of the treatment did not associate with PFS and OS. Conclusions: Outcomes of LEN and ATZ/Bev treatment for advanced HCC were not different in pathologically confirmed MASLD. Longer OS of LEN than ATZ/Bev was observed in the patients with relatively better liver function, suggesting that LEN might be a suitable first-line treatment for HCC with compensated liver function in the patients with pathologically confirmed MASLD.
The efficacy of adjuvant chemotherapy after total mesorectal excision with selective lateral pelvic node dissection for lower rectal cancer.
Authors: Kameishi Shin , Yamaguchi Toshifumi , Hamamoto Hiroki , Okemoto Dai , Kadono Toru , Yukami Hiroki , Goto Masahiro , Nishikawa Hiroki
Published: January 2024

50

Background: The standard strategy for lower rectal cancer (LRC) is neoadjuvant chemoradiotherapy (CRT) plus total mesorectal excision (TME) in Western countries. TME with or without lateral pelvic node dissection (LND) followed by adjuvant chemotherapy is the standard treatment for LRC in Japan. However, the efficacy of adjuvant chemotherapy for LRC after TME without LND remains unclear. The aim of this study was to assess the efficacy of adjuvant chemotherapy for LRC after TME without LND. Methods: We retrospectively reviewed patients who underwent R0 resection by TME without LND and received adjuvant chemotherapy between 2010 and 2020 at our institution. The inclusion criteria were as follows: age ≥ 20 years; histologically confirmed adenocarcinoma; pathological stage III (UICC 8th); lower rectal cancer (Ra/Rb); patients who received adjuvant chemotherapy after R0 resection without LND and no prior treatment before surgery. We evaluated relapse free survival (RFS) and overall survival (OS) in patients with LRC. Prognostic impact of location, adjuvant chemotherapy regimens, T factor, and N factor on RFS was explored by a multivariate analysis. Results: From a total of 197 patients, 117 patients were eligible. Median age was 65 years (range 26–82) and 54 patients (46%) were male. Tumor location was 67 (57%)/50 (43%) for Ra/Rb and pathologic stage was 47(40%) /61(52%)/ 9(8%) for IIIA/IIIB/IIIC. Eighty patients (68%) received fluoropyrimidine monotherapy (single agent) and 37 patients (32%) received oxaliplatin based therapy (doublet) as adjuvant chemotherapy. The 3-year RFS rate and 3-year OS rate were 70.7% (95% CI, 59.0-81.1%) and 94.5% (95% CI, 89.0-98.1%). The 3-year RFS rates according to tumor location (Ra/Rb) and adjuvant chemotherapy regimen (single agent/doublet) were 76.9%/70.7% and 71.8%/68.5%, respectively. The 3-year RFS rates based on pathological stage (IIIA/IIIB/IIIC) were 76.7%/68.4%/64.8%. In a multivariate analysis, T3/4 were identified as an independent poor prognostic factor for RFS (p<0.05). Conclusions: TME without LND followed by adjuvant chemotherapy for patients with LRC demonstrated favorable 3-year RFS rate. adjuvant chemotherapy regimens after TME without LND suggested no additive efficacy of oxaliplatin on RFS.
Initial uptake of durvalumab with or without tremelimumab for advanced hepatocellular carcinoma in routine clinical practice: Preliminary results of the international DT-real study.
Authors: Celsa Ciro , Nishida Naoshi , Arvind Ashwini , Ulahannan Susanna Varkey , Li Michael , Scheiner Bernhard , Fulgenzi Claudia A.M. , D'Alessio Antonio , Manfredi Giulia F , Stefanini Bernardo , Cabibbo Giuseppe , Cortellini Alessio , Pinter Matthias , Kelley Robin Kate , El Tomb Paul Antoine , Singal Amit G. , Kudo Masatoshi , Pinato David James
Published: January 2024

501

Background: HIMALAYA trial showed that durvalumab plus tremelimumab (Single Tremelimumab Regular Interval Durvalumab; STRIDE) significantly improved overall survival (OS) and that durvalumab (DUR) was non-inferior compared to sorafenib in patients with hepatocellular carcinoma (HCC). However, real world outcomes on this regimen have not been described. Methods: In the context of a prospectively maintained database including 953 patients (pts) with unresectable HCC treated with immunotherapy, we analysed a subgroup of pts treated with STRIDE or DUR across 5 centres in USA, Asia and Europe. We assessed OS, progression-free survival (PFS), objective response rate (ORR) by RECIST 1.1 (per investigator) and treatment-related adverse events (TRAEs) per CTCAE v.5.0. Results: Between February and May 2023, 59 pts initiated treatment with STRIDE or DUR (mean age 67.2 years, male sex 81.4%). 33 pts (55.9%) were treated in first-line (1L) and 26 (44.1%) in second- or further-line (>1L). STRIDE regimen was administered in 24 patients (40.7%): 6 pts in 1L, 18 pts in >1L. Child-Pugh class was A in 32 pts (54.2%), being more common in pts treated with STRIDE than DUR (79.2% vs 37.1%, p=0.003). ECOG-PS was 0 in 35 pts (59.3%) and it was more common in pts treated with STRIDE than DUR (79.2% vs 47.0%, p=0.015). Outcomes are reported in Table. After a median follow-up of 3.2 months (95%CI 2.6-3.8), median OS was not reached and 6-month OS rate was 59.4%. In pts treated with STRIDE, median OS was not reached and 6-month OS rate was 95.8%, while median OS was 4.9 months (95%CI 3.2-4.9) for DUR. Median PFS was 2.5 months (95% CI 1.9-3.8) and ORR (evaluable in 43 pts, 72.9%) was 16.3% (95%CI 6.5-33.5%). Any grade TRAEs and grade 3-4 TRAEs were 42.4% (95%CI 27.4-62.5) and 10.2% (95%CI 3.7-22.1%), respectively. TRAEs requiring systemic corticosteroid therapy occurred in 3 pts (5.1%). Conclusions: Preliminary observational data from DT-real confirm uptake of STRIDE and DUR across various lines of therapy, with encouraging efficacy and safety outcomes in routine practice. [Table: see text]
The interim analysis of a single-arm, open-label, phase II study investigating ALLEN regimen (durvalumab plus albumin paclitaxel and lenvatinib) in patients with unresectable biliary tract cancers (BTCs).
Authors: Li Zhifang , Chen Meixia , Ming Qianyi , Zhang Yan , Feng Kaichao , Mei Qian , Liu Yang , Han Weidong
Published: January 2024

504

Background: BTCs are a heterogeneous group of malignancies with a poor prognosis. Despite the improved outcome achieved by the addition of the anti-PD-L1 antibody durvalumab to standard chemotherapy, the benefits were modest and cannot satisfy the clinical demands adequately. This study aimed to evaluate the efficacy and safety of the combination therapy of Albumin paclitaxel, Durvalumab and Lenvatinib (ALLEN regimen) in unresectable BTCs. Methods: This single-arm, single-center, open-label, phase I/Ⅱ study enrolled patients with locally advanced or metastatic BTCs. Eligible patients with ECOG score 0-2 were treated with ALLEN regimen. Durvalumab (1000mg IV, q3w) in combination with albumin paclitaxel (180-220 mg/m2 IV q3w) and lenvatinib (8mg PO QD) were given regularly until disease progression. The primary endpoint was objective response rate (ORR) evaluated by investigators according to RECIST 1.1. The secondary endpoints were disease control rate (DCR), progression-free survival (PFS) and treatment-related adverse events (TRAEs). Results: From September 2021 to September 2023, fourteen patients were enrolled including three patients who were failed to prior anti-PD-1 antibody treatment. The median follow-up was 6.8 months (95% CI 1.9, 10.9). The median age of the patients was 59.0 years, and male patients accounted for 35.7%. The ORR and DCR were 35.7% and 100%, respectively. The median PFS was 7.3 months (95% CI 4.9, 8.2). TRAEs of any grade occurred in 13 (92.9%) patients without grade 3 or higher. The most common TRAEs were alopecia (13/14, 92.9%), peripheral sensory neuropathy (10/14, 71.4%), decreased appetite and nausea (9/14, 64.3%), hypertension (6/14, 42.9%), rash (5/14, 35.7%), diarrhoea (4/14, 28.6%), and asthenia (4/14, 28.6%). Conclusions: The ALLEN regimen demonstrated encouraging anti-tumor activity with a tolerable safety profile in unresectable BTCs. The preliminary results were promising, which deserved further investigation in a larger population. Clinical trial information: NCT05327582 .
Evaluating local tumor destruction and wedge or segmental resection in the treatment of fibrolamellar hepatocellular carcinoma: An NCDB analysis.
Authors: Bine Christopher Reese , Braaten Marco , Czaplicki Alec , Nielsen Eric G. , Lee Aron , Silberstein Peter T.
Published: January 2024

512

Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare type of hepatic cancer, comprising 1% of all liver malignancies. Patients are often diagnosed in their second or third decade and often have a palpable liver mass. Treatment primarily consists of surgery and transplant, however, standardized protocols have not been well established due to its rarity. For patients who cannot receive a transplant, there are few studies examining and comparing other surgical types. Using the National Cancer Database, we aim to uncover survival and patient characteristic differences between those who receive Local Tumor Destruction vs Wedge or Segmental Resection. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with FL-HCC from 2004 to 2019 using the histology codes 8171 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at α = 0.05. Results: Of the 803 patients in the sample,19 patients received Local Tumor Destruction (LTD) and 142 patients received Wedge or Segmental Resection (WSR). The average age of patients receiving LTD was 54 compared to 32 for WSR. WSR patients experienced longer overall survival than LTD (106 vs. 63 months respectively; p<0.05). When controlling for age, year of diagnosis, tumor size, comorbidity score, and surgery type, WSR showed a greater decrease in overall hazard compared to LTD (HR=0.224 vs 0.306; p<0.05). WSR use was highest in healthy patients with no co-morbidities, however, patients were also significantly more likely to have later stage tumors (II, III, and IV vs. stage I; p<0.001). Despite being associated with a lower OS, LTD was utilized more commonly for earlier stage (stage I vs. II, III and IV; p<0.001) and well differentiated tumors (p<0.001). Compared to WSR, it was associated with higher rates of therapy before and after surgery(p<0.05). There were no significant differences in tumor size, income group, adjuvant therapy type, or facility type (p>0.05) between the treatment groups. Conclusions: Receipt of WSR is associated with improved survival compared to LTD. There are distinct demographic groups which may be guiding surgical selection. Further research into this disparity and other surgical types should be examined to create better guidelines for FL-HCC patients.