bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMbrave150: Exploratory analysis to examine the association between bevacizumab (bev) ever being skipped and bev never being skipped in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab (atezo) + bev in a global phase 3 study.
Authors: Kudo Masatoshi , Tsuchiya Kaoru , Shao Yu Yun , Finn Richard S. , Galle Peter R. , Ducreux Michel , Cheng Ann-Lii , Yamashita Tatsuya , Koga Hironori , Aoki Kenichi , Yamada Kyoko , Asakawa Takashi , Nakagawa Yuki , Ikeda Masafumi 
Published: January 2023

538 Background: Treatment with atezo + bev has been approved globally for patients with unresectable HCC who have not received prior systemic therapy, based on results from the Phase 3 IMbrave150 study (NCT03434379, Finn NEJM 2020 and Cheng J Hepatol 2022). According to Phase 1b study data (Lee Lancet Oncol 2020), when combined with atezo, bev has a clinically relevant contribution in terms of immune enhancement and normalization of tumor blood vessels. However, it is unknown if bev being skipped due to bev adverse events of special interest (AESIs) has an impact on the efficacy of atezo + bev. Here, we conducted an exploratory efficacy analysis examining patients who had skipped bev vs those who never skipped bev using IMbrave150 study data. Methods: In Arm A of IMbrave150, patients were assigned to receive atezo + bev. Group A-1 included patients whose bev was ever skipped due to bev AESIs. Group A-2 included the patients who were not included in group A-1. Landmark analyses of overall survival (OS) and progression-free survival (PFS) were performed in patients who received atezo + bev for ≥6 months to minimize immortal time bias. Results: Of 210 patients who received ≥6 months of atezo + bev, 69 were assigned to group A-1 and 141 were assigned to group A-2. No obvious differences between groups were observed in the distribution of baseline characteristics. Of the group A-1 patients, 75.4% were BCLC stage C and 76.8% were Child-Pugh A5, while group A-2 patients were 80.1% BCLC stage C and 77.0% were Child-Pugh A5. At the data cutoff (Aug 20, 2020), median OS was 25.8 vs 26.2 months (HR, 1.04; 95% CI: 0.64, 1.69) and median PFS per independent review facility-assessed RECIST 1.1 was 15.5 vs 10.0 months (HR, 1.07; 95% CI: 0.74, 1.55) for groups A-1 and A-2, respectively. Conclusions: The patients who had ever skipped bev did not show different efficacy compared with those who had never skipped bev in this post hoc analysis. Although limitations due to the non-randomized and exploratory nature of this comparison should be acknowledged, the results suggest that skipping bev did not have considerable impact on the efficacy of atezo + bev. Clinical trial information: NCT03434379 .
The efficacy of capecitabine as a salvage treatment in metastatic colorectal cancer after prior 5-fluorouracil–included chemotherapies.
Authors: Jang Jae Yeon , Bang hyun-Jin , Bae Woo Kyun , Lee Seung-Shin , Lee Soonil , Shim Kwang Yong , Kong Jee Hyun , Kim Yundeok , Lim Seungtaek 
Published: January 2023

54 Background: We aimed to retrospectively analyze the efficacy and toxicity of capecitabine, as a salvage treatment, in metastatic colorectal cancer (mCRC) that progressed after prior standard 5FU included chemotherapies. Methods: From January 1, 2008, to December 31, 2017, patients with mCRC, age ≥ 18, who received capecitabine as third- or fourth-line treatment at five different centers in South Korea, were included. All had disease progression on prior palliative chemotherapies including 5FU, oxaliplatin, and/or irinotecan. Results: A total of 131 patients were analyzed with a median age of 62 (range, 35-87). Almost all patients were exposed to prior 5FU (100%), irinotecan (100%), and oxaliplatin (98.5%). Patients were treated with cetuximab (26.7%), or bevacizumab (45.8%) before capecitabine. The median and mean duration from the last 5FU exposure to capecitabine start were 21 and 67.3 days, respectively (range, 5-1322). The objective response rate (ORR) of capecitabine was 3.6%, and the disease control rate was 30.4%. The median progression free survival (mPFS) and median overall survival (mOS) was 2.77 (95% CI, 2.495-3.045) and 9.60 months (95% CI, 7.625-11.575), respectively. There was a significant difference in efficacy according to the duration from the last 5FU exposure to the time of starting capecitabine. Compared to patients who started capecitabine earlier than 67 days after the last 5-FU administration, those who started capecitabine later than that time showed higher ORR (11.1% vs 1.2%; p-value = 0.043), mPFS (4.430 (95% CI, 2.274-6.586) vs 2.570 months (95% CI, 2.326-2.814); p-value = 0.011), and mOS (14.070 (95% CI, 5.627-22.513) vs 9.500 months (95% CI, 7.370-11.630, p-value = 0.021) (Table). 68.7% patients experienced any grade of adverse events, but only 4.6% complained grade 3 or higher. There was no treatment related death. Conclusions: Capecitabine showed modest antitumor activity with good tolerability in mCRC patients whose disease progressed after oxaliplatin and/or irinotecan. It could be considered as an alternative treatment option for mCRC patients, especially for those who have longer treatment free interval after 5FU based chemotherapies. [Table: see text]
Pertuzumab plus trastuzumab (P+T) in patients (pts) with biliary tract cancer (BTC) with ERBB2/3 amplification (amp), overexpression (oe), or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.
Authors: Cannon Timothy Lewis , Rothe Michael , Garrett-Mayer Elizabeth , Chiu Vi Kien , Hwang Jimmy J. , Vijayvergia Namrata , Alese Olatunji B. , Dib Elie G. , Duvivier Herbert Leon , Klute Kelsey , Sahai Vaibhav , Ahn Eugene R , Behl Deepti , Sinclair Sarah , Thota Ramya , Urba Walter John , Yang Eddy Shih-Hsin , Grantham Gina N. , Halabi Susan , Schilsky Richard L. 
Published: January 2023

546 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pts with BTC with ERBB2/3 amp, oe, or mut treated with P+T are reported. Methods: Eligible pts had advanced BTC, no standard treatment (tx) options, measurable disease, ECOG Performance Status (PS) 0-2, and adequate organ function. Genomic testing was done in CLIA-certified, CAP-accredited labs. Dosing of P was 840 mg IV over 60 minutes (m), then 420 mg IV over 30-60 m Q3 weeks (wks); T was 8 mg/kg IV over 90 m, then 6 mg/kg IV over 30-60 m Q3 wks until disease progression. Primary end point was disease control (DC), defined as complete (CR) or partial (PR) response per RECIST v. 1.1, or stable disease (SD) at 16+ wks (SD16+). Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 has DC, 18 more pts are enrolled; otherwise, cohort is closed for futility. If ≥7 of 28 pts has DC, the null DC rate is rejected. Secondary end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), duration of SD and safety. DOR is defined as time from pt’s first documented objective response (OR) to progressive disease (PD). Duration of SD is defined as time from start of tx to PD. Results: 29 pts with BTC (15 gallbladder (GB), 11 biliary duct (BD), 3 ampulla of Vater) and ERBB2/3 amp, oe, or mut were enrolled from Feb 2017 to Jan 2022. Median (med) age was 66 years (yrs) (range, 34-83 yrs). 66% of pts were female; 52% were White, 21% were Black/African American, 10% were Asian/Asian American; 83% were not Hispanic or Latino. 83% of pts had ECOG PS 0-1 and 48% had ≥3 prior systemic regimens. 1 pt was not evaluable and excluded from efficacy analysis. The table shows efficacy outcomes. 1 pt had CR (GB; ERBB2 amp; DOR: 71.1 wks), 8 pts had PR (6 GB/2 BD; 5 ERBB2 amp; 2 ERBB2 mut; 1 ERBB3 mut/ ERBB2 amp; med DOR: 30.4 wks (4.4 to 68.9 wks)) and 2 pts had SD16+. 4 pts with a KRAS mut did not achieve OR or SD16+. 4 pts had a Grade 3 drug-related adverse or serious adverse event (SAE): anemia, diarrhea, infusion related reaction (SAE), and fatigue. Conclusions: P+T demonstrated antitumor activity in pts with advanced BTC with ERBB2/3 alterations. These data, along with results previously reported by other studies, support continued study of P+T in pts with ERBB2 amplified BTC tumors. Clinical trial information: NCT02693535 . [Table: see text]
Comparison of clinical features by primary sites in patients with biliary tract cancer who received gemcitabine-based chemotherapy: An exploratory analysis of JCOG1113.
Authors: Suzuki Yuko , Morizane Chigusa , Mizusawa Junki , Sano Yusuke , Kobayashi Satoshi , Imaoka Hiroshi , Terashima Takeshi , Ikeda Masafumi , Okano Naohiro , Sugimori Kazuya , Todaka Akiko , Shimizu Satoshi , Mizuno Nobumasa , Sekimoto Mitsugu , Sano Keiji , Tobimatsu Kazutoshi , Katanuma Akio , Okusaka Takuji , Ozaka Masato , Ueno Makoto 
Published: January 2023

548 Background: Biliary tract cancers (BTCs) include gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), and ampulla of Vater cancer (AV). Although it was previously reported that there were differences in clinical features individually, the reported data were limited to data from some subgroup analyses of recent randomized controlled trials. JCOG1113 (UMIN000010667) showed the non-inferiority of gemcitabine plus S-1 to gemcitabine plus cisplatin in terms of overall survival (OS) in patients (pts) with advanced BTCs. We aimed to compare clinical features among the primary sites of BTCs using JCOG1113 data. Methods: Among the 354 pts enrolled in JCOG1113, 352 pts were included in this analysis except for 2 pts without BTCs. We compared the patient characteristics and treatment outcomes, such as OS, progression-free survival (PFS), and objective response rate (ORR), among the four primary sites. Results: Of the 352 pts, 137 pts (38.9%), 94 pts (26.7%), 108 pts (30.7%) and 13 pts (3.7%) had GBC, IHCC, EHCC, and AV, respectively. GBC was more common in females (58.4%) than males, in contrast to the other primary sites. The percentage of pts with metastatic disease for GBC was the highest (78.1%) and involved multiple metastatic organs (41.6%), in contrast with the other primary sites. The median OS for GBC, IHCC, EHCC and AV were 12.6 months (reference), 15.7 months (hazard ratio [HR]; 0.749, 95% confidence interval [CI], 0.559-1.005), 16.3 months (0.704, 0.532-0.934) and 11.5 months (1.148, 0.633-2.080), respectively. The median PFS for GBC, IHCC, EHCC and AV were 5.7 months (reference), 6.2 months (0.843, 0.644-1.104), 8.7 months (0.636, 0.489-0.826) and 4.1 months (1.506, 0.851-2.665), respectively. The ORRs for GBC, IHCC, EHCC and AV were 34.4%, 28.9%, 34.4%, and 0.0%, respectively. Conclusions: Except for AV which included a few patients in this trial, GBC showed a poorer prognosis compared with the other primary sites. Furthermore, it was more likely to include metastatic disease and multiple metastases, and this is likely one of the causes of the poorer prognosis. [Table: see text]
Presence and impact of antidrug antibodies (ADAs) to tremelimumab (T) or durvalumab (D) in the phase 3 HIMALAYA study of unresectable hepatocellular carcinoma (uHCC).
Authors: Crysler Oxana V. , Yarchoan Mark , Furuse Junji , Galle Peter R. , Sukeepaisarnjaroen Wattana , Thinh Nguyen Tien , Masi Gianluca , Lim Ho Yeong , Varela Maria , Gupta Charu , Makowsky Mallory , Negro Alejandra , Abou-Alfa Ghassan K. 
Published: January 2023

551 Background: ADAs to immune checkpoint inhibitors may decrease antitumor activity in HCC. Reported rates of treatment-emergent ADAs (TE-ADAs) vary from 1.5% for pembrolizumab and 8.6% for nivolumab to 54.1% for atezolizumab across indications (Enrico et al. Clin Cancer Res 2020). In the global, Phase 3 HIMALAYA study (NCT03298451) in uHCC, the STRIDE regimen (Single T Regular Interval D) significantly improved overall survival vs sorafenib (S); D monotherapy was noninferior to S (Abou-Alfa et al. NEJM Evid 2022). Here, we analyzed ADAs to T and D in HIMALAYA. Methods: Prespecified secondary analyses assessed the presence of ADAs to D and T before the first study dose (baseline), once during treatment and once after treatment discontinuation. For participants (pts) who were ADA-positive at any visit (ADA+), presence of neutralizing antibodies (nAbs) was also assessed. TE-ADA+ was defined as pts with a positive post-baseline sample only or pts with an ADA titer that increased ≥4-fold following treatment. ADA negative (ADA-) was defined as pts with no positive sample at any visit, at baseline or post-baseline. Objective response rate (ORR; RECIST v1.1, inc. unconfirmed), overall survival (OS) and treatment-related adverse events (TRAEs) were evaluated in ADA subgroups. Results: The frequency of ADAs to D was similar in the STRIDE (T+D) and D arms: 8.2% (24/294) and 7.1% (20/282) of pts, respectively, were ADA+ to D; 3.1% (9/294) and 2.8% (8/282) of pts, respectively, were TE-ADA+ to D; and 1.7% (5/294) and 0.7% (2/282) of pts, respectively, had nAbs to D. In the STRIDE arm, 15.9% (29/182) of pts were ADA+ to T, 11.0% (20/182) of pts were TE-ADA+ to T, and 4.4% (8/182) of pts had nAbs to T. Although the number of pts was small, in the STRIDE arm, ORR was 11.1% (1/9) in pts TE-ADA+ to D, 35.0% (7/20) in pts TE-ADA+ to T and 23.9% (94/393) in the full analysis set (FAS). In the D arm, ORR was 25.0% (2/8) in pts TE-ADA+ to D and 18.5% (72/389) in the FAS. OS for pts TE-ADA+/nAb+ to D or T in the D and STRIDE arms was consistent with the FAS. In both arms, TRAE and Grade 3/4 TRAE rates were not increased in the ADA+ vs ADA- groups (Table) and were generally consistent with the overall population. Conclusions: In HIMALAYA, the rates of TE-ADAs and nAbs to D and T were low (≤11%). The presence of ADAs did not appear to impact clinical efficacy or safety of STRIDE or D monotherapy in the small number of ADA+ pts. These results support a low risk of ADAs for STRIDE or D in uHCC. Clinical trial information: NCT03298451 . [Table: see text]
Efficacy of nivolumab and ipilimumab in patients with hepatocellular carcinoma with prior immune-checkpoint inhibitor treatment.
Authors: Cheon Jaekyung , Kang Beodeul , Jung Sang-Hoon , Kim Chan , Chon Hongjae 
Published: January 2023

554 Background: Nivolumab plus ipilimumab (NIVOIPI) demonstrated promising efficacy in patients with unresectable hepatocellular carcinoma(uHCC) in the phase 1/2 CheckMate 040 trial. However, as atezolizumab plus bevacizumab (Ate/Bev) is a new first-line standard systemic therapy, it is necessary to evaluate the role of NIVOIPI after treatment with Ate/Bev. Methods: Patients with uHCC who received NIVOIPI after previous systemic treatment were included. Patients received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks (four doses), followed by nivolumab (240 mg) every 2 weeks. Patients with Child B/C class and BCLC D stage uHCC were excluded. Patients who had at least one follow-up visit after the start of NIVOIPI were included. Results: A total of 47 patients were included with characteristics as follows: median age of 60 years (range, 37–79); hepatitis B (n = 40, 85.1%), hepatitis C (n = 2, 4.3%), non-viral (n = 5, 10.5%); BCLC B/C (n = 2, 4.3%; n = 45, 95.7%); macrovascular invasion (n = 12, 25.5%); extrahepatic metastasis (n = 41, 87.2%); and AFP ≥ 400 ng/ml (n = 26, 55.3%). Thirty-five (74.5%) patients had a history of prior immune-checkpoint inhibitor (ICI) treatment (n = 35, 74.5%), including Ate/Bev (n = 23, 48.9%). According to the RECIST 1.1, 12 patients achieved a partial response, resulting in an overall response rate (ORR) of 25.5% and disease control rate (DCR) of 42.6%. The ORR and DCR were 41.7% and 58.4% in ICI-naïve patients and 20.0% and 37.1% in patients with prior ICI treatment. The median follow-up duration was 5.7 months (95% confidence interval [CI], 5.4–6.1), the median progression-free survival was 1.4 months (95% CI, 1.1–1.7) in all patients, 1.3 months (95% CI, 0.1–1.1) in prior ICI-treated patients and was not reached in ICI-naïve patients. The median overall survival was not reached. The most common grade 3–4 toxicities were aspartate aminotransferase elevation (n = 4, 8.5%), neutropenia (n = 4, 8.5%), skin toxicity (n = 3, 6.4%), alanine transaminase elevation (n = 2, 4.3%) and pneumonitis (n = 2, 4.3%). There was one treatment-related death due to toxic epidermal necrolysis. Conclusions: NIVOIPI demonstrated clinical meaningful efficacy in patients with uHCC, with and without prior ICI treatment.
Multisite institutional study of efficacy and safety of cabozantinib following immunotherapy in patients with advanced hepatocellular carcinoma.
Authors: Palmer Mathias Earl , Storandt Michael H. , Gile Jennifer , Zemla Tyler J. , Bekaii-Saab Tanios S. , Jin Zhaohui , Tran Nguyen H. , Mahipal Amit 
Published: January 2023

559 Background: Cabozantinib, a multikanase inhibitor, is approved by the Food and Drug Administration (FDA) for treatment of advanced stage hepatocellular carcinoma (HCC) following progression on sorafenib. The CELESTIAL study which demonstrated benefit from cabozantinib following sorafenib included only patients with Child Pugh class A liver function. Recently, bevacizumab plus atezolizumab has replaced sorafenib as the first line treatment for HCC. It is unclear whether there is benefit from using Cabozantinib following progression on immunotherapy as CELESTIAL trial included very few patients who received prior immunotherapy. We describe the outcomes of individuals with advanced stage HCC treated with Cabozantinib following progression on immunotherapy. Methods: This was a multicenter, retrospective analysis of patients with advanced HCC diagnosed between 2010-2021 at Mayo Clinic Arizona, Florida, and Minnesota. Progression free survival (PFS) and median overall survival analysis were performed using Kaplan-Meier method. Results: We identified a total of 26 patients with advanced stage HCC who received cabozantinib following progression on immunotherapy. The median age of patients was 61 years (range, 39 – 81) and the majority were male (85%). Eighteen (72%) patients had Child Pugh A at initiation of cabozantinib therapy. Four (15%) patients received cabozantinib as second line therapy, the rest received it as third line or later. PFS on cabozantinib was 2.1 months (95% CI: 1.3 – 3.9) and median overall survival from time of cabozantinib initiation was 7.7 months (95% CI: 5.3 – 14.9). PFS was shorter with Child Pugh Class B, 1.3 months (95% CI: 0.9 – NE) compared to those with Child Pugh Class A, 2.1 months (95% CI: 1.5 – 4); although this difference was not significant (p=0.55). Common adverse events included fatigue (50%), anorexia (35%), aspartate aminotransferase (AST) elevation (35%), and diarrhea (31%); 7 (26%) patients experienced Grade 3 or greater adverse events including hypertension, diarrhea, anorexia, and bowel obstruction. Two patients discontinued cabozantinib due to side effects including one for uncontrolled blood pressure elevations and the other due to fatigue. Conclusions: The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy is unknown. Treatment with cabozantinib may improve clinical outcomes following progression on immunotherapy with similar adverse event profile. This study included patients with Child Pugh class B liver disease (28%) and heavily pretreated population and demonstrated mPFS and mOS similar to other work examining outcomes of cabozantinib in real world setting after progression on sorafenib. Further studies to determine optimal treatment sequencing for this patient population are needed.
Real-world use of biologics and its association with outcomes in RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC) in Canada.
Authors: Cheung Winson Y. , Boyne Devon J. , Brenner Darren R. , Martinez Daniel , Wani Rajvi J. , Ngan Elaine 
Published: January 2023

56 Background: The use of biologics in combination with chemotherapy early in the course of treatment in mCRC improves outcomes, but whether this approach is uniformly adopted in clinical practice is unclear. This study aims to describe biomarker testing, treatment patterns, and survival of RAS WT, left-sided mCRC patients in a real-world population. Methods: We performed deterministic linkages with population-based data sources, including the cancer registry, pharmacy data, electronic medical records, and vital statistics to identify all patients who were diagnosed with RAS WT, left-sided mCRC, and treated with first-line (1L) combination systemic therapy from 2014 to 2019 in Alberta, Canada. Patients were followed until December 31, 2020. Results: Of 2,721 patients with left-sided mCRC, 1,375 were referred and received systemic therapy, 977 underwent RAS testing prior to or within 30 days of initiating 1L treatment, and 420 were found to be RAS WT. Among them, 320 were treated with 1L combination systemic therapy: FOLFOX/CAPOX/FOLFIRI (n=204), panitumumab (pani) with doublet chemotherapy (n=64), or bevacizumab (bev) with doublet chemotherapy (n=52). The interval from diagnosis to RAS test results was 38 (IQR 24-61) days. Only 207 (65%) and 125 (39%) of the 320 1L-treated patients reached 2L and 3L therapy, respectively. Median overall survival based on the different 1L regimens are summarized. Conclusions: Many real-world patients with mCRC were not exposed to biologics as part of their front-line treatment. There is a need to enhance RAS testing in 1L as 29% of patients were not tested, despite recommendations from guidelines. Because attrition across lines of therapy is high in mCRC, the opportunity to receive and benefit from biologics in later lines of therapy may be importantly reduced. [Table: see text]