tbuckley/cabot-search huggingface dataset:
HLX22 plus HLX02 and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer: A randomized, double-blind, multicenter phase 2 study.
Authors: Jin Li, Yong Gao, Ning Li, Meng Qiu, Yan-Qiao Zhang, Mudan Yang, Linzhi Lu, Wei Li, Yuntao Ma, Xiaoming Hou, Guoping Sun, Mingquan Cai, Jingran Wang, Jianwei Lu, Diansheng Zhong, Futang Yang, Jing Li, Qingyu Wang, Jun Zhu
Journal: Journal of Clinical Oncology (2024)

354 Background: Gastric/gastroesophageal junction (G/GEJ) cancer represents a global healthcare challenge. With more than 1 million new cases estimated in 2020, it ranked fifth among all cancers. HER2 amplification or overexpression were reported in around 20% of advanced G/GEJ cancer cases. Despite the improved overall survival with trastuzumab plus chemotherapy, the prognosis remains unsatisfactory, and thus more effective treatments are needed. This study aimed to evaluate the combination of HLX22 (a novel anti-HER2 monoclonal antibody), HLX02 (a trastuzumab biosimilar), and chemotherapy for patients with G/GEJ cancer in the first-line setting. Methods: The study was unblinded 3 months after the last patient was enrolled. Patients with locally advanced or metastatic HER2-positive G/GEJ cancer and had not received prior systemic antitumor therapy were enrolled. The study consisted of 2 parts; current report will focus on part 1. In part 1, patients were randomized 1:1:1 to receive HLX22 25 mg/kg + HLX02 + XELOX (group A), HLX22 15 mg/kg + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were PFS and ORR assessed by IRRC per RECIST v1.1. Secondary endpoints included other efficacy measures and safety. Results: As of July 30, 2023 (data cutoff), 53 patients were randomized to group A (n=18), B (n=17), and C (n=18), and were followed up for a median of 14.3 months. 44 (83.0%) patients were male. Main efficacy results are presented in Table. Tumor assessments reported in Table were performed by IRRC. Treatment-related adverse events (TRAEs) occurred in 18 (100.0%), 16 (94.1%), and 17 (94.4%) patients in the respective groups. Serious TRAEs were observed in 5 (27.8%) patients in group A, 1 (5.9%) in group B, and 1 (5.6%) in group C. Only 1 (5.6%) patient in group C had a grade 5 TRAE. Conclusions: Adding HLX22 to HLX02 + XELOX improved survival and antitumor response in patients with HER2-positive G/GEJ cancer in the first-line setting, with a manageable safety profile. Clinical trial information: NCT04908813 . [Table: see text]
Trends in utilization of MSI testing and reporting among patients with gastrointestinal cancers: A review of NCDB Database.
Authors: Baqir Jafry, Munir Buhaya, Emina Huang, Nilesh Verma, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2024)

221 Background: MSI-H tumors have a different disease biology and clinical outcomes compared to MSS/MSI-low tumors. The frequency and pattern for MSI testing and reporting is unknown. The aim of this study was to characterize the trends of MSI testing and reporting among GI cancers. Methods: From the National Cancer Database, we identified all GI cancer patients from 2010 to 2016 to determine the number of patients where MSS/MSI low or MSI-H data were available. We describe the basic tumor and disease characteristics and treatment utilization for the two groups. Results: Between 2010-2016, MSI testing was done in 140,602 patients in colon, small intestine and rectal cancers among all GI cancers. MSI testing increased significantly during this study period (11,400 in 2010; 15,021 in 2011; 17,968 in 2012; 20,810 in 2013; 21,973 in 2014; 25,012 in 2015; 28,418 in 2016). We identified a total of 120,349 patients with MSI status reported, among these three tumor types, most commonly among colon followed by rectal and then small intestinal cancers. Overall 111,694 (92.8%) were MSS/MSI-low and 8,655 were MSI-H (7.2%). Among patients with reported MSI status, 52.1% were males and 47.9% were females. The mean age was 64.4 years. Most patients were whites (87.6%) and had insurance (96.8%), no existing comorbidities (70.4%), and grade 2 (70.8%) and AJCC Clinical Stage 4 (26.1%) GI cancer. A higher proportion of GI cancer patients with MSS/MSI-low utilized chemotherapy as first course compared to those with MSI high (48.2% vs 34.0%) whereas a lower proportion of GI cancer patients with MSS/MSI-low underwent a surgical procedure compared to those with MSI high (94.7% vs 97.1%). MSI status was reported most frequently in comprehensive community cancer program (40.3%) and academic center (34.8%), followed by integrated network cancer program (16.8%) and Community Cancer program (8.1%). Conclusions: The utilization of MSI testing has increased significantly between 2010 and 2016. Among all GI cancer patients, MSI status was most frequently reported in colon, rectum and small intestinal cancers. Comprehensive community cancer centers and academic centers reported MSI status more frequently than Integrated Network Cancer program and Community Cancer program.
Advances in the treatment of gastroenteropancreatic poorly differentiated neuroendocrine carcinoma at our hospital.
Authors: Shinichi Nishina, Mitsuru Yokota, Yoshio Nagahisa, Kenji Kawata, Michio Okabe, Toshihiko Masui, Kazuyuki Kawamoto
Journal: Journal of Clinical Oncology (2024)

595 Background: Overall survival after first-line chemotherapy for metastatic or recurrent gastroenteropancreatic poorly differentiated neuroendocrine carcinoma (GEP-NEC) is reported to be less than 1 year. Platinum drugs in combination with etoposide or irinotecan have been used as first-line chemotherapy for GEP-NEC patients, but no standard treatment has been established for second-line and subsequent chemotherapy. Recently, however, we have seen patients with a good prognosis after treatment based on comprehensive cancer genomic profiling (CGP). We retrospectively reviewed GEP-NEC patients treated with chemotherapy. Methods: Patient background, treatment regimen, overall survival, and toxicity were evaluated in 20 GEP-NEC patients who started first-line platinum combination chemotherapy at our hospital between October 2016 and September 2022. Results: Median age was 71 (48 to 81) years, 16 were male, and primary sites were esophagus in 2 patients, stomach in 7 patients, small intestine in 2 patients, large intestine in 6 patients, and pancreas in 3 patients. Five patients had an adenocarcinoma component. Stage III, IV, and recurrence were observed in 2, 16, and 2 patients, respectively. Progression-free survival and overall survival after first-line chemotherapy were 4.0 (2.3 to 7.0) and 8.1 (4.7 to 17.0) months, respectively. Grade 3 or higher toxicity was observed in 13 patients. No differences in overall survival were observed in chemotherapy regimen including etoposide or irinotecan and cisplatin or carboplatin. Patients who underwent CGP had significantly longer survival. After second-line chemotherapy, a regimen containing irinotecan, 5-FU, paclitaxel, ramucirumab, and nivolumab was used, and overall survival was 5.2 (1.8 to NA) months. There were 4 of 20 patients who survived for more than 1000 days after first-line chemotherapy. Durable responses were observed in colonic NEC patients harboring the POLE P286R mutation treated with nivolumab and in those harboring the BRAF V600E mutation treated with cetuximab and encorafenib. Conclusions: Overall survival of GEP-NEC patients treated with platinum combination chemotherapy was very poor at only 8 months. However, in some cases, long-term survival has been achieved with molecular targeted therapy based on CGP results.
HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer (mCRC) refractory to anti-EGFR antibodies.
Authors: Atsushi Ishiguro, Hiroshi Nakatsumi, Kazuaki Harada, Satoshi Yuki, Kentaro Sawada, Susumu Sogabe, Takayuki Ando, Yusuke Sasaki, Ayumu Yoshikawa, Michio Nakamura, Masayoshi Dazai, Miki Tateyama, Osamu Muto, Masahito Kotaka, Tamotsu Sagawa, Kazuteru Hatanaka, Ryo Takagi, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2024)

113 Background: Aflibercept (AFL) combined with FOLFIRI prolongs overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) who failed a prior oxaliplatin-based regimen. However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI in RAS / BRAF wild type pts previously treated with anti-epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese pts with mCRC failing a prior oxaliplatin-based chemotherapy combined with an anti-EGFR agent. Methods: This was a prospective open-label phase II trial. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5-FU 400 mg/m2 and infusional 5-FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression-free survival (PFS) rate at 6 months; secondary endpoints included OS, PFS, overall response rate (ORR), disease control rate (DCR), adverse events, and relative dose intensity (RDI) for each drug. Given a PFS rate threshold at 6 months of 38.9% and an expected PFS rate of 58.4% with AFL plus FOLFIRI, a sample size of 41 pts was required (two-sided alpha, 0.1; beta, 0.2). Analyses were conducted in the full analysis set (FAS) of pts satisfying eligibility criteria. Results: Forty-three patients were enrolled between November 2019 and October 2022, and 43 were analyzed (median age 68 years (range 27-80); male, 69.8%; ECOG PS 0/1, 72.1%/27.9%; left sided primary tumor, 90.7%). The primary endpoint was met: 6-month PFS rate was 58.7% (90%CI, 45.5%-71.9%). Median PFS and OS were 7.3 months (95%CI, 5.5-11.0 months) and 18.8 months (95%CI, 12.9-26.6 months), respectively. The ORR was 23.3 % (95%CI, 11.8-38.6%) and DCR was 88.4% (95%CI, 74.9- 96.1%). Mean RDI of AFL, irinotecan, bolus 5-FU and infusional 5-FU were 75.3% (SD, 26.2), 50.6% (SD, 12.5), 31.6% (SD, 26.6), and 58.7% (SD, 7.21), respectively. The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%) and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. Conclusions: Results of this prospective phase II study suggest that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese pts with mCRC who failed a first-line oxaliplatin-based plus anti-EGFR regimen. Clinical trial information: jRCTs011190006 .
Real-world use of pemigatinib (pemi) for cholangiocarcinoma (CCA) among racial and ethnic minorities in the United States.
Authors: Richard D. Kim, Cherrishe Brown-Bickerstaff, Angele Kotomale, Michael A. Rodriguez, Bruce A. Feinberg, Sarah Gordon, Kristin M. Zimmerman Savill, Haobo Ren, Michael Blecker, Kim Saverno
Journal: Journal of Clinical Oncology (2024)

461 Background: Pemi received accelerated approval by the FDA in 2020 for treatment of patients (pts) with unresectable locally advanced or metastatic CCA with a fibroblast growth factor receptor 2 ( FGFR2) fusion or other FGFR2 rearrangement. A recent real-world study (RWS; submitted to ASCO-GI 2024) assessing characteristics, FGFR2 testing patterns, treatment patterns, and outcomes of pts treated with pemi for locally advanced or metastatic CCA in the US as part of routine clinical care found substantial racial and ethnic diversity in pts treated with pemi. The purpose of this analysis is to describe the findings of the pemi RWS for CCA by race and ethnicity. Methods: This was a retrospective cohort study in which US-based participating physicians from Cardinal Health’s Oncology Provider Extended Network abstracted data from eligible pts’ medical records into electronic case report forms. Eligible pts were ≥18 years of age, initially prescribed pemi for unresectable locally advanced or metastatic CCA on or after 4/17/2020, and had ≥4 mo of follow-up (unless &lt;4 mo due to death). Pts who did not receive pemi or had received pemi in a clinical trial or systemic therapy for another primary malignancy (except for cancer of unknown primary or hepatic cancer) were excluded. Results were summarized by race (White, Black/African American, “Other” [pts with mixed race or a race other than White, Black/African American, or Unknown]) and ethnicity (Non-Hispanic, Hispanic) using descriptive statistics. Results: 18 physicians abstracted data for 120 eligible pts. Median follow-up from initial pemi prescription was 6.5 mo, at which time 71 pts (59%) were alive and 60 (50%) were still receiving pemi. The racial makeup of the study population was 55% White, 21% Black, 18% Other, and 7% Unknown. Ethnic composition was 78% Non-Hispanic, 19% Hispanic, and 3% Unknown. Key results are presented in the Table. Conclusions: The diverse population in this RWS is reflective of the heterogeneous CCA pt population in the US. These real-world overall response rates support the clinical benefit of pemi across racial and ethnic groups and complement the results of the clinical trial. [Table: see text]
Second-line regorafenib in patients (pts) with unresectable hepatocellular carcinoma (uHCC) after progression on first-line atezolizumab plus bevacizumab (Atezo-Bev): Phase 2 REGONEXT trial.
Authors: Changhoon Yoo, Jaekyung Cheon, Baek-Yeol Ryoo, Min-Hee Ryu, Hyung-Don Kim, Kyu-Pyo Kim, Beodeul Kang, Hong Jae Chon, Richard S. Finn
Journal: Journal of Clinical Oncology (2024)

477 Background: Atezo-Bev is the standard first-line therapy against uHCC. However, there is no globally established subsequent treatment after failure on first-line Atezo-Bev. We aimed to evaluate the efficacy and safety of second-line regorafenib in uHCC pts who progressed on first-line Atezo-Bev. Methods: This is a phase II investigator-initiated trial involving 2 academic centers in Korea. Key eligibility criteria include confirmed diagnosis of HCC; prior treatment with Atezo-Bev at least ≥ 2 cycles; Child-Pugh A; ECOG performance status 0-1. Eligible patients received regorafenib 160 mg once daily 3 weeks on/1 week off until progressive disease or intolerable toxicity. The primary endpoint is progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR) according to the RECIST v1.1, overall survival (OS) and treatment-related adverse event (TRAE). Results: Total 40 pts were recruited from Dec 2021 to May 2023. Pts characteristics were as follows: median age of 56 (range, 36-81); hepatitis B (77.5%), hepatitis C (10.0%), non-viral (12.5%); BCLC C stage (97.5%); and AFP ≥ 400 ng/ml (40.0%). As of the date of data cut-off (15 Aug 2023), the median follow-up duration was 6.6 mo (95% CI, 5.0-8.2). The median PFS was 3.5 mo (95% CI, 3.0-4.0). ORR and DCR were 10.0% and 82.5%. The median OS was 9.7 mo (95% CI, 8.3-11.1) and 6-month OS rate was 55.0%. The median OS since the start of prior Atezo-Bev was 16.6 mo (95% CI, 11.9-21.3). When stratified according to the duration of prior Atezo-Bev (&lt;4 cycles [n=10] vs. ≥4 cycles [n=30]), pts with ≥4 cycles of prior Atezo-Bev showed better median OS (not reached vs 3.6 mo; p=0.001) and ORR (13.3% vs 0%; p=0.009), while there was a trend for better median PFS (3.8 mo vs 2.5 mo; p=0.107). The most common grade 3-4 TRAEs were thrombocytopenia (5.0%), palmar-plantar erythrodysesthesia (2.5%), and fatigue (2.5%). Conclusions: Regorafenib was effective as second-line therapy in uHCC pts who progressed on first-line Atezo-Bev. Efficacy and safety outcomes from our study were consistent with those observed in the pivotal phase 3 RESORCE trial which included sorafenib-tolerated/progressed pts. Clinical trial information: NCT05134532 .
Real-world evaluation of clinical outcomes and long-term survivors in patients with BRAF-V600E metastatic colorectal cancer.
Authors: William Phillips, Mohammad Alrehaili, Horia Marginean, Tim Asmis, Michael M. Vickers, Bryan Lo, Rachel Anne Goodwin
Journal: Journal of Clinical Oncology (2024)

166 Background: BRAF-V600E mutant metastatic colorectal cancer (BRAF-V600E mCRC) is associated with poor prognosis but confers response to combination BRAF/EGFR blockade. The goal of this study is to evaluate the clinicopathologic features and natural history of BRAF-V600E mCRC in the era prior to combination BRAF/EGFR inhibitors. Methods: This is a retrospective study of patients treated at the Ottawa Hospital Cancer Centre with BRAF-V600E mCRC who did not receive combination BRAF/EGFR therapy. Patients diagnosed with colorectal cancer prior to March 31, 2021, were included. Demographic, clinical, pathologic and cancer characteristics were abstracted from electronic medical records. Outcomes of interest included duration of therapy, as a surrogate of progression free survival, and overall survival (OS). Long-term survivor was defined as OS greater than 2 years. Results: 74 patients were included. Median age was 70 years (IQR=61-78), and 39 (53%) patients were female. There were 17 (23%) patients alive at the end of the follow-up period. 31 (42%) patients had poorly differentiated grade and 26 (35%) were mismatch repair deficient (dMMR). Locations of metastases included liver (40, 54%), peritoneum (30, 41%), lung (18, 24%), bone (5, 7%) and brain (5, 7%). Overall, 64 (86%) patients received first line systemic therapy, 19 (26%) second line, and 5 (7%) third line (see Table). Median duration of therapy in the first line was 4.3 months (IQR=2.0-9.6), second line was 2.9 months (IQR=1.4-4.1), and third line 1.0 months (IQR=1.0-1.9). Overall survival in the entire cohort was 13.2 months (IQR=4.6-25.4). Importantly, 21 (28%) patients were long-term survivors, of which 8 (11%) were dMMR. Conclusions: Patients with BRAF-V600E mCRC generally have poor clinical outcomes with traditional systemic therapies. In this study, we identified approximately 25% of patients who are long-term survivors (OS &gt;2 years). This reflects the real-world heterogeneity of clinical outcomes for patients with BRAF-V600E mCRC who did not receive BRAF/EGFR targeted therapy.[Table: see text]
Patient factors and survival outcomes of pancreatic signet cell carcinoma: A comprehensive review and analysis.
Authors: Aron Lee, Christopher Bine, Alec Czaplicki, Eric Nielsen, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2024)

608 Background: Pancreatic signet cell carcinoma is an aggressive, rare subtype of pancreatic adenocarcinoma that constitutes less than 1% of all pancreatic cancers. This subtype can manifest as solitary cells or a cluster within the background of pancreatitis, often leading to an incorrect diagnosis during biopsies. The rarity and challenges associated with its diagnosis significantly impact its poor prognosis. With an average age of diagnosis of 67.3 years and a median life expectancy of 12.6 months, there exists a lack of information on the disparities that exist in these patients and how patient demographics contribute to differences in survival outcomes. Methods: We used the National Cancer Database to identify patients diagnosed with pancreatic signet ring cell carcinoma (ICD-O-3 histology code 8490) between 2004-2019 (N=1746). Survival was evaluated using Kaplan-Meier curves and log-rank tests. Significance was set at p&lt;0.05. Results: When analyzing insurance status, patients with private insurance had a statistically improved survival outcome (14.3 months) compared to those with Medicare (11.3 months), Medicaid (9.2 months) and without insurance (11.8 months) (p&lt;0.05). Patients with private insurance had fewer positive regional lymph nodes (73), lower grade/differentiation (5.80) and an average tumor size of 444.40 millimeters. Patients treated at academic research programs had a statistically better survival outcome (15.1 months) compared to patients treated at comprehensive community (10.4 months) and integrated network (9.1 months) programs (p&lt;0.001). Surgical treatment had statistically improved survival outcomes compared to non-surgical treatment (p&lt;0.001) with the majority of these procedures being a partial pancreatectomy and duodenectomy with a partial gastrectomy. More patients received surgical intervention at academic research programs (p&lt;0.001), and patients with private insurance predominately attended academic research programs (p&lt;0.001). Conclusions: Factors associated with increased survival outcomes include insurance status, positive regional lymph nodes, grade/differentiation, treatment facility type and surgical intervention. These findings make a valuable contribution to the ongoing research on disparities affecting survival in patients with pancreatic signet cell carcinoma.
MRD assay to evaluate recurrence and response via a tumor informed assessment: MARIA-Colorectal Cancer Observational trial.
Authors: Edward D. Esplin, Kelli Swan, Lee Ifhar, Brandie Heald, Sarah M. Nielsen, Daniel Esteban Pineda Alvarez, William D. O'Callaghan, Robert Daber, Darrel Ross, Carlos Vieira, W. Michael Korn, Aadel A. Chaudhuri
Journal: Journal of Clinical Oncology (2024)

TPS242 Background: The detection of ctDNA in patients with colorectal cancer (CRC) is emerging as a potential biomarker to identify patients at high risk of relapse, assess treatment response and monitor for recurrence. Solid tumors are currently monitored by imaging studies, tumor markers and clinical symptoms and recent studies suggest tumor-informed molecular residual disease (MRD) testing may outperform these current methods and may serve as a prognostic biomarker to aid in the identification of patients at high risk of relapse (Reinert et al, 2019; Christensen et al, 2019; Coombes et al, 2019). Recent studies have demonstrated that tumor-informed MRD testing can detect relapse prior to detection with imaging in CRC and while interventional trials are needed, this may provide an opportunity for therapeutic intervention (Reinert et al, 2019; Kotani et al, 2023). This study utilizes the Invitae Personalized MonitoringTM (PCM) test, a highly sensitive tumor-informed MRD test (Zhao et al, 2023), to monitor early stage CRC patients. Methods: MARIA is a multi-site, prospective, observational trial in the United States of 200 newly diagnosed patients with early stage (high risk stage II, stage III and stage IV oligometastases) CRC undergoing curative intent treatment. Formalin fixed paraffin embedded (FFPE) tissue from the biopsy or surgical specimen is utilized to create the PCM test. Tumor tissue and a matched normal blood sample will undergo whole exome sequencing to identify 18-50 unique tumor variants to create a patient specific panel (PSP) for ctDNA analysis. Participants are asked to provide serial plasma specimens for ctDNA analysis at baseline, post surgical landmark and surveillance time points. A clinical report will be provided to the ordering physician. Physicians will be asked to complete a case report form for each participant when the first result is reported and every 6 months. The primary endpoint is to evaluate the correlation between the PCM test result at the landmark timepoint and the patient’s 24 month recurrence risk. Secondary endpoints include evaluating the impact on patient outcomes attributable to MRD result-based changes to treatment or clinical management, correlating between the PCM result at the baseline time point and patient recurrence risk and outcomes and investigating the lead time of PCM positivity over clinical/imaging based evidence of recurrence. Active enrollment started in March, 2022. Clinical trial information: NCT05219734 .